Race organisers said Simoncelli was sent to the medical centre at the Sepang circuit for treatment but efforts to revive him were unsuccessful.
“He was already unconscious when the medical team arrived,” said MotoGP medical director Michele Macchiagodena.
“We attempted to resuscitate him but failed. He died 45 minutes later.”
The race, the second to last of the season, was cancelled. Simoncelli died a week after Indianapolis 500 winner Dan Wheldon was killed in a 15-car accident in the IndyCar finale at the Las Vegas Motor Speedway.
Simoncelli lost control of his Honda at turn 11, four minutes into the race, but his bike regained partial grip and swerved across the track and into the path of American Colin Edwards and Italian Valentino Rossi.
Simoncelli’s helmet was ripped off in the collision and he lay motionless on the track. He had been fourth at the end of the first lap.
Race director Paul Butler said circumstances surrounding Simoncelli’s accident would be investigated.
“We had our standard operating procedure,” he said.
“This is one-of-a-kind freak incident where the helmet came off and I am sure [motorcycling body] FIM and MotoGP will be looking into this.”