The crash was reported at about 12:30 p.m. near the off-ramp to 19th Avenue.
A Toyota Rav4 traveling south on Doyle Drive crossed into northbound traffic for unknown reasons and sideswiped a northbound Mercedes Benz, California Highway Patrol Officer Chris Rardin said.
The collision caused the Mercedes to veer into southbound traffic and crash into a Subaru, Rardin said.
Meanwhile, the Rav4 rolled onto its side in the northbound lanes and was hit by a Chevrolet Aveo, he said.
Five people were taken to San Francisco General Hospital by ambulance, he said.
The CHP initially reported that the crash caused only minor injuries, but Rardin said he has since clarified that the driver of the RAV4 suffered pelvic and rib fractures and a punctured lung.
Rardin said everyone involved was wearing a seat belt.
"It's proof positive that seat belts save lives," he said.
The entire roadway was shut down for about 20 minutes after the crash, and for a while only one northbound lane was open.
Lanes were cleared at about 1:50 p.m. and traffic began flowing normally again.