The little lad, affectionately known as 'Wee Oscar' by the thousands of people who have followed his journey over the last few years, passed away on Thursday afternoon.
His parents mounted a social media campaign after his diagnosis with neuroblastoma at the age of two, in a bid to raise funding and awareness for treatment.
Back in April last year, Oscar had been given the all-clear, but sadly the cancer returned a few months later.
In a tweet on Friday, Stephen and Leona told those who had supported them: "Our beautiful, amazing and much loved son Oscar James Knox gained his angel wings yesterday afternoon."
In a statement, the family said they were incredibly proud of Oscar and how he had lived his life and asked for privacy over the coming days.
"It is with heartbreaking sadness that we wish to share the news that our beautiful amazing and much loved son Oscar James Knox, born on 10 September 2008, has gained his angel wings," they said.
"Oscar has brought unimaginable joy to our family with his smile and his infectious personality.
"Our little superhero achieved so much in his short life and inspired so many people throughout the world to do so many amazing things, something we are incredibly proud of.
"We wish to take this opportunity once again to thank all of Oscar's followers the world over for everything they have done for us and for the wonderful kindness and generosity that has been shown.
"We also want to thank the teams at The Royal Belfast Hospital for Sick Children and NI Children's Hospice whose kindness and compassion has been nothing short of amazing.
"Nothing can ever take the pain away but knowing we were supported so much and that Oscar was loved so much, brings great comfort."
Oscar, our angel, forever our SuperHero.
The family added: "This is a heart breaking time for us and we would respectfully ask for privacy in the coming days.
"We would also like to take this opportunity to ask that any donations be made in lieu of flowers or toys.
"Donations, which will be shared between the NI Children's Hospice and the Haematology Unit at The Royal Belfast Hospital for Sick Children, can be made via a dedicated JustGiving page at www.justgiving.com/oscarknox.
"A donation of £5 can also be made by texting KNOX55 £5 to 70070."
Thousands of pounds have already been donated in a matter of hours.
Last year, Oscar's inspirational courage saw him awarded the overall Spirit of Northern Ireland award, which was presented to him by his friend and Olympic boxer Paddy Barnes.
A host of sport stars and other famous faces have been won over by Wee Oscar - from the First and Deputy First Minister to WWE stars like the Rock and Triple H.
Oscar's ability to unite communities, including in support of events like blood drives in his name, was never more apparent than when he visited the First and deputy First Ministers at Stormont.
In his little shirt and tie, he quickly put Peter Robinson and Martin McGuinness in their places, taking over their offices before presenting them each with a handprint painting.
A picture of the smiling leaders setting aside political differences to pose with Oscar between them, an arm firmly around their necks, spoke volumes.
Sending their thoughts and prayers to the Knox family - Stephen, Leona and Oscar's little sister Isobella - they both spoke of their sadness at the loss.
"When I met Oscar, I was struck by his infinite energy and sense of fun. He had a tremendous capacity to overcome the challenges he and his family faced together," Mr Robinson said.
"Oscar was an amazing little boy who lived his life to the full and filled those around him with admiration and hope. He will be deeply missed by everyone who met and loved him."
Mr McGuinness added: "The day Oscar and his family visited Stormont was one of my most uplifting days in politics and you couldn't help but be enthused by his vibrancy and spirit.
"Oscar was a little warrior who faced down sickness and setbacks and showed all of us how precious life is."
Boxer Carl Frampton, who donned a Team Oscar t-shirt after winning his big fight that could pave the way for a shot at a world title, spoke to UTV about his sadness on hearing the news.
"I knew he was very, very, very ill, but it's still a shock that he's passed away. Because he's such a fighter, you kind of expect him to come through it and to get better," he said.
Speaking about Oscar's fondness for their mutual friend Paddy Barnes, Carl revealed that the loss was particularly poignant at this time.
"Oscar loved Paddy. And Paddy's celebrating the birth of his daughter yesterday and then the wee man has died on the same day ..." he said.
"Sometimes words like 'inspiration' can be overused, but it definitely fits well with Oscar Knox.
"Obviously the family will be heartbroken - but they should be proud of what a fighter they had, the inspiration he is to us all, and proud of themselves for the awareness they raised."
Even football rivalries were laid aside for Oscar, with both Rangers and Celtic showing their support.
Lurgan-born Celtic boss Neil Lennon said supporters who had known about Oscar's story were devastated to hear the news.
"He fought so hard to keep going, so it will have touched a lot of people today," he said.
As a Hoops fan, the little lad had been delighted to get his chance at being a mascot when the team hosted Cliftonville in the Champions League in Glasgow last July - even getting serenaded by the visitors.
"That showed the affection that our fans had for Oscar and that was replicated right across the football family, through every sport, household and family in the country," Cliftonville chairman Gerard Lawlor said.
"Everyone at Solitude offers deep, heartfelt condolences to Oscar's family and I hope they find strength in the fact that the people of our football club represent just a fraction of the numbers around the world who are thinking of and praying for them at this very difficult time."
Other teams, including Linfield and Glentoran, have also backed Team Oscar over the years.
Oscar's funeral, which the family want to be a colourful celebration of his life, is to be held on Sunday.
Following the private wake, a Mass of Angels will be held at St Bernard's Church in Glengormley at 11am.
People are being encouraged to join a procession from the hospice which will begin at 10.15am and move on to St Bernard's Church.
The family have said that everyone is welcome to attend and they are encouraging people to wear bright colours.