The driver, a woman, was the only occupant of the car, CHP Officer Jaret Paulson said.
She was to be flown to Santa Rosa Memorial Hospital but was diverted to St. Helena Hospital and died either there or on the way, Paulson said.
Three occupants of the pickup suffered unknown injuries and were taken to Queen of the Valley Medical Center in Napa, Paulson said.
The accident was reported around 10 a.m. south of Bale Lane. Silverado Trail was closed at 10:08 a.m. but reopened at 11:49 a.m., the CHP said.