Emergency crews were called to the scene between junctions 5 and 6 of the M5 in Worcestershire on Monday afternoon.
West Midlands Ambulance Service was called out at 1.26pm. Two ambulances, a paramedic officer, and the Midlands Air Ambulance from Strensham attended the scene.
A West Midlands Ambulance Service spokeswoman said: “Crews arrived at the scene to find the driver of the car in a critical condition after coming into collision with an HGV.
“Crews worked quickly to administer advanced trauma care to the woman. But sadly, despite their best efforts, nothing could be done to save her, and she was confirmed deceased on scene.”