Boss Fred Done will give a guaranteed £100,000 to Royal Manchester Children's Hospital but hopes to raise a lot more.
The cash is being used to fund state-of-the-art intra-operative Magnetic Resonance Imaging (iMRI) equipment to help kids with brain tumours, traumatic brain injuries and other problems.
The fundraising effort is personal for Done, 76, who lost wife Mo last year after she was diagnosed with a brain tumour.
He said: "It is humbling I'm in a position to help with this appeal for much-needed equipment.
"From my own sad experience, I know how important it is to have world-class equipment available to help save the lives of your loved ones.
"I feel privileged I can help, and I do hope the best scanner money can buy will end up saving the lives of seriously ill children brought to Manchester from all over the country."
Betfred will donate all profits from other bets that day too, including Man City's Champions League match against Schalke.
Done added: "It's anything we win over the counter in the shops, whether it's football, dogs, anything.
"It's what we win less the tax and levy – and if the government want to say we don't want the tax I'll hand that over too!
"Last year we had a bad first day but I've guaranteed a minimum of £100,000, and there's no cap on what the shops can produce for them.
"Nobody knows what the results are going to be but if we get the right results we might be handing over a handsome cheque, that's all I can say."
For more information about the appeal, or to donate, visit www.rmchcharity.org.uk/imri-appeal.
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