The accident was reported around 8 pm Saturday.
A white Toyota Highlander appears to have struck the pedestrian on the freeway, said CHP Officer Bert Diaz.
He could not immediately say whether the victim is a man or a woman.
It wasn't immediately apparent why the pedestrian was on the freeway, Diaz said. No one in the Highlander was injured.
All lanes of southbound I-280 at Cesar Chavez remained closed as of 9 pm Saturday.