The California Highway Patrol says the crash happened just before 9 a.m. Tuesday on Avenue 11 and Road 33 1/2.
That's just south of the Madera Ranchos.
Officers say the woman was driving eastbound in a Toyota Camry and failed to stop at a stop sign.
Her car was hit by a Chevy pickup truck.
The woman was taken to Community Regional Medical Center with major injuries.
Officers say the man driving the pickup had a complaint of pain.
Stay with ABC30 for the latest details on this developing story.