The single-car crash occurred at around 2:37 a.m. on the southbound side of the freeway, just west of the 605 Freeway, according to the California Highway Patrol.
The car was moving at an unknown high rate of speed when the driver lost control, causing the vehicle to slam into a guardrail and bridge abutment of the Lemonran Avenue pedestrian over-crossing.
The car split in two upon impact.
Two rear passengers were ejected onto the right shoulder of the roadway, and rear portion of the vehicle came to rest about 100 feet south of the front portion of the car.
The driver and front passenger were still in the car when it became fully engulfed in flames.
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Firefighters responded to the scene and quickly extinguished the fire.
All four occupants of a Dodge Charger were pronounced dead at the scene.
The deceased driver and passengers were not immediately identified.
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The cause of the crash is under investigation by the CHP. Two southbound lanes were closed by Caltrans as crews worked to clear the wreckage from the freeway.