It happened on the A1079, between Wilberfoss and Barmby Moor, at around 1.15pm this afternoon (Friday) and involved a black Peugeot 207, a white Renault Estate panel van and a white Ford Transit tipper truck.
Humberside Police are at the scene and say two men suffered what are thought to be serious injuries.
A spokesperson added: "The road is currently closed and motorists are advised to avoid the area."