The collision was reported at 8:50 p.m. on Christmas Tree Point Road.
Three pedestrians there were struck by a sedan and knocked from the road onto the hillside, police said.
A fourth pedestrian managed to jump out of the way, sustaining minor injuries, police said.
All four pedestrians were evacuated from the scene by paramedics using ropes and backboards and were taken to a hospital.
One of the pedestrians, a woman possibly in her 50s is being treated for life threatening injuries.
The suspect vehicle, a silver or gray sedan was located a short distance away and police have detained the driver.
One occupant in the suspect vehicle complained of injury and was transported to a local hospital, police said.
Officers will evaluate the driver to determine if sobriety was a factor in the collision.
Anyone with information about the crash has been asked to call San Francisco police at (415) 553-1641.