The accident led to a huge fire which shut two major highways, CBS Station KCBS reports.
The tanker-truck's load of fuel ignited when it went over an embankment.
The trucker sustained second- and third-degree burns to 75 percent of his body in Friday's accident, California Highway Patrol Officer Denise Medina said.
"I just saw this guy come out of the truck fully engulfed in flames and just running," witness Vanessa Juarez said. "His whole body was on fire."
The 44-year-old man was airlifted to University of California, Irvine, Medical Center and was listed in critical condition early Saturday.
The motorist, burned beyond recognition, was found in the wreckage of a car more than an hour after the crash, authorities said.
The truck, carrying 5,000 gallons of diesel and 3,000 gallons of gasoline, overturned at around 9 p.m. on northbound Interstate 5 about 30 miles southeast of downtown Los Angeles, the Highway Patrol said.