The 2006 MotoGP World Champion was cycling in eastern Italy when he collided with a car five days ago.
Former MotoGP champion Nicky Hayden has died five days after the American was hit by a car while cycling in eastern Italy, his Honda World Superbike team said in a statement on Monday.
"It is with great sadness that Red Bull Honda... has to announce that Nicky Hayden has succumbed to injuries suffered during an incident while riding his bicycle last Wednesday," the team said.
"Nicky passed away at 19.09 (local time) this evening at Maurizio Bufalini hospital in Cesena. His fiancee Jackie, mother Rose and brother Tommy were at his side."
The 35-year-old had been in intensive care with severe brain damage since he was struck by a car while training on his bicycle along Italy's Adriatic Coast.
The force of the impact shattered the car windscreen.
Tributes across the world
MotoGP promoters Dorna joined in tributes from across the world of motorsport for the 'Kentucky Kid' who won the 2006 world title for Honda.
"A true Champion on and off track, Hayden will be deeply missed," they said.
"Hayden will be deeply missed by the paddocks he has graced throughout an incredible career, his millions of fans around the world, and by all those closest to him."
The last medical bulletin from the hospital, dated May 20, said Hayden remained in a critical condition. The hospital had previously said he had suffered serious brain damage in the accident.
Hayden last raced in the MotoGP championship in Spain in September 2016 as a stand-in for injured Australian Jack Miller at the privately-run Marc VDS Honda team. He started 216 races between 2003 and 2015, winning three.
"Although this is obviously a sad time, we would like everyone to remember Nicky at his happiest - riding a motorcycle," said his brother Tommy in the team statement.
"He dreamed as a kid of being a pro rider and not only achieved that but also managed to reach the pinnacle of his chosen sport in becoming world champion. We are all so proud of that."
Italian newspapers reported on Monday that investigators had found video of the accident from a camera on a house overlooking the road.
They said the images suggested Hayden had failed to stop at an intersection and was hit full on by the passing car.
There was no immediate confirmation of the report from the investigators.