The What Makes You Beautiful hitmaker donated the acoustic instrument to Kean's Children's Fund in Dundee, Scotland, along with an autograph and personal message.
The charity's owner, Charlie Kean, hopes to raise $32,000 (£20,000) for his young patients by auctioning the guitar online.
He says, "The boys from One Direction really do support the charity but it's really Zayn and his mum Tricia that are always keen to lend a hand.
"I got a call from Zayn on (the) Sunday before the boys left for America and Tricia posted the guitar this week. I hope we'll get around £20,000. But the band have some really dedicated fans, so who knows?"
The boyband is currently in South America on the Where We Are stadium tour.