It happened just before 4:30 a.m. Friday at Shoemaker Boulevard.
According to authorities, the driver hit the center divider along the eastbound lanes of the 91 and was ejected.
That's when a semi-truck hit the car.
The California Highway Patrol says the driver was pronounced dead on the scene.
As of 6 a.m., the eastbound lanes of the freeway were shut down.
Motorists are urged to take an alternate route as authorities continue their investigation.