The Bangor band announced they had to cancel their first festival headline gig after singer, Alex Trimble, was deemed too ill to perform.
They issued a statement which read: "It is with a heavy heart that we are going to need to cancel our upcoming shows at Latitude and Bournemouth Academy.
"Alex collapsed at Seattle airport on the way to London and has been hospitalised with a chronic stomach complaint.
"We are devastated to have to cancel shows that we were so looking forward to. We can only apologise and hope for your understanding at this time."
After being announced as their replacement, Lily Allen sent her best wishes to Trimble, but said she was looking forward to taking to the stage at Henham Park.
She said: "So sorry to hear about Alex from Two Door Cinema Club. However I am more than happy to step in.
"I've never been to Latitude but I hear it's fabulous and I can't wait to get my heels on for some serious dancing action on Friday evening - so, so excited."
Melvin Benn, managing director of Festival Republic which runs the event, said he was sad that Two Door Cinema Club had been forced to cancel their performance "under advice of doctors".
He added: "We wish Alex all the best and a speedy recovery.
"We are honoured that Lily Allen is able to step in at the last minute and would like to thank her for filling the headline slot.
"After her show-stopping performance at Glastonbury Lily was a natural choice, the Latitude audience are in for something really spectacular."