Emergency services rushed to the collision on junction 14 just before midnight on Monday to cut the man out of the wreckage.
He was treated for serious head and chest injuries by paramedics.
Images from the scene appear to show the mangled front of a silver car after it smashed into the rear of a truck as the busy orbital road splits into the M40.
A Met spokesman said: “Police and LAS were called to the M25 at junction 14 following reports of a collision involving an HGV and a car.
“The driver of the car was taken to hospital where he remains.
“His injuries have been assessed as life threatening.”
A London Ambulance spokesman said: “We treated a patient at the scene for head and chest injuries and took him to a major trauma centre as a priority.”
A London Fire Brigade spokesman added: “A car and a lorry were involved. One person who was trapped was released by fire crews and taken to hospital by London Ambulance Service crews.
“The Brigade was called at 12.01am and the incident was over for firefighters by 12.35am. Fire engines from Heathrow and Hayes fire stations and a fire and rescue unit from Heston Fire Station attended the scene.”
Road closures are in place in the clockwise lanes and, as of 8am, there was a mile of congestion approaching Junction 14.
Drivers are being encouraged to avoid the area and allow for extra travel time this morning.
A Highways England spokesman said: “Metropolitan Police and National Highways Traffic Officers remain on scene. London Fire Brigade and London Ambulance Service attended.”
The police are conducting accident investigation work with more tailbacks expected on the A30, A308, A4 and M4.