The crash happened on the A39 between Arch Hill and Kea Church in Truro, Cornwall, at about 11:00 BST on Friday.
The man, who had been driving a Vauxhall Corsa, suffered "serious life threatening injuries" and was taken to hospital, police said.
Part of the A39 was shut after the crash, involving a red Vauxhall Corsa, a white Peugeot Motor Caravan, a blue Volkswagen Tiguan and a blue BMW 3.
A man in his 80s has died after being in a car crash involving four vehicles.