The motorway was closed in both directions as police dealt with the incident which happened on the eastbound carriageway near to the Cranford Park interchange at 11.39am on Sunday.
A Metropolitan Police spokesman said that one man, believed to be aged in his 20s, died at the scene while two other men were taken to hospital with “life-threatening injuries”.
A fourth casualty was treated for minor injuries before being taken to hospital.
A post on social media showed a car on fire at the side of the motorway as someone used a fire extinguisher in an attempt to put out the flames.
Another post showed firefighters dealing with the car after the fire had been put out.
The police force spokesman said: “Officers are appealing for witnesses and any dashcam footage following a fatal collision on the M4 in west London.
“At 11.39am on Sunday 29 October, officers were called to reports of an overturned car on the eastbound M4 near to the Cranford Park Interchange.
“Emergency services attended and four people were found with injuries, all of whom had been travelling in the car, a Mercedes.
“A man, thought to be aged in his 20s, died at the scene. He was a passenger in the rear of the car. We are in the process of informing his next of kin.
“Two other men, also thought to be aged in their 20s, were taken to hospital with life-threatening injuries.
“A fourth person was treated at the scene for minor injuries before being taken to hospital.
“Officers from the Met’s Roads and Transport Policing Command are carrying out inquiries to establish the circumstances.”
A London Ambulance Service spokesman said: “We were called at 11.34am today to reports of a road traffic collision on the M4, Hayes.
“We sent a number of resources to the scene, including three ambulance crews, an advanced paramedic, an incident response officer, a clinical team manager, members of our hazardous area response team and our tactical response unit.
“We also dispatched London’s Air Ambulance.
“We treated three patients at the scene before taking them to a major trauma centre. Very sadly, a person was pronounced dead at the scene.”