The brave four-year-old from Belfast had recovered from a rare form of the disease but was recently told the heartbreaking news that he had fallen ill again.
It prompted an outpouring of well-wishes on Friday from thousands of people who have been captured by Oscar's inspirational story.
In a message on Twitter, the family responded: "OVERWHELMING msgs flooding in, thank you all so much for your kind words and fighting spirit.
"If only love could mend our baba... #TeamOscar."
Oscar's family went public with his battle with neuroblastoma after medics revealed he was suffering from the aggressive condition in November 2011.
His mum Leona and dad Stephen shared the good news in April that he was cancer-free.
But writing in their blog on Thursday night, Leona said they found out a week ago while they were in Scotland that the cancer had returned.
Please, please send every positive thought you have our way and support our brave wee Oscar as he fights for his life once more.
"We've had some terrible news - Oscar's cancer has returned, the disease is extensive, and it's spreading rapidly," she wrote.
"We saw the full extent of it in the scans he had today. It's not good, we are totally heartbroken and very frightened about what lies ahead."
Leona said that little Oscar is not eating or drinking and is finding it difficult to walk.
The family are trying to manage his pain, which she described as "excruciating", with morphine and they are deciding on a treatment plan.
"We have some very difficult choices to make, but more importantly Oscar has ANOTHER incredibly tough battle on his hands," she added.
Leona and Stephen said they are shocked, scared and overwhelmed, but thanked everyone for their support so far.
Oscar has battled this disease once and won. All at UTV wish him and his family well in the days and weeks ahead.
Michael Wilson, UTV MD, in his blog
Oscar received a standing ovation at a ceremony in June as he was presented with the main Spirit of Northern Ireland Award, where he was joined onstage by long term supporter Belfast boxer Paddy Barnes.
"Oscar touches the hearts and minds of everyone in Northern Ireland and, when he won the Sunday Life Spirit of Northern Ireland award, everyone was in tears in the room," Sunday Life editor Martin Breen said.
"Everyone gets behind him and will continue to get behind him.
"Oscar that night said he had won the game and that is why he picked up his award - I think we all hope and pray that Oscar will win this latest game."
Reacting to the news on Friday, many well-known figures were among the hundreds sending messages of support and sympathy.
In a message to Oscar on Twitter, Olympic boxing medallist Barnes said: "Beat it once, (you'll) beat it again."
Martin McGuinness told followers on Twitter that Oscar's visit to the Stormont Executive office "was one of the most uplifting days ever".
DUP Junior Minister Jonathan Bell said: "Thoughts and prayers with Oscar Knox his parents and family circle a brave inspirational young boy praying for his healing."
Recently, Oscar received a huge warm welcome at Celtic home ground when he was a mascot for their Champions League clash with Cliftonville and the Scottish giants have posted a message of support on their official website, hailing the little lad for his "incredible courage and bravery".
The statement adds: "The thoughts and prayers of everyone at the club, and indeed, the entire Celtic family are with Oscar, his parents Stephen and Leona, and all his family at this very difficult time."
Rangers footballer Kyle Hutton simply posted "PrayforOscar" on his Twitter account.
Local clubs have also expressed their support for the little football fan.