The crash happened around 2:20 a.m. when a driver ran a red light at the intersection of Cesar Chavez and Folsom streets, broad-siding another car, according to San Francisco police Officer Gordon Shyy.
The force of the crash sent one of the cars into a third vehicle, leaving that driver with minor injuries.
Shyy said the driver of the broadsided car suffered life-threatening injuries and was taken to San Francisco General Hospital. Meanwhile, the driver and multiple passengers from the car that ran the red light ran from the scene, Shyy said.
One occupant of that car stayed at the scene and is being interviewed by investigators.
The investigation into the crash is ongoing and anyone with information is asked to call San Francisco police at (415) 701-2311.