Luis Mendoza of La Puente was pronounced dead after he and his sons, ages 13 and 16, were transported to a hospital, according to the California Highway Patrol.
Mendoza's official cause of death was not immediately released, and it was unclear if the two boys were injured by gunfire or the crash, or both.
The CHP was summoned to a multi-vehicle crash at 12:28 p.m. Saturday on the eastbound 60 Freeway, just east of Crossroads Parkway, a news release said.
Arriving officers found a white Chevrolet Avalanche pickup truck with extensive damage from colliding with a white Kia and a concrete retaining wall, the Highway Patrol said.
The three victims were taken to Los Angeles County-USC Medical Center, where Mendoza was pronounced dead.
The 13-year-old suffered major head injuries and the 16-year-old suffered injuries that were not life-threatening, the CHP said.
Witnesses told the CHP the front passenger of a silver or gray compact vehicle in the HOV lane pointed a handgun out of the window and fired several shots at Mendoza's truck, causing him to lose control and slam into the Kia and the retaining wall. The sole occupant of the Kia was not hurt.
A description of the shooter was not available.
Anyone with information about the shooting is urged to call the CHP at (323) 259-3200 or CHP Major Crimes at (323) 644-9550.