The crash happened just before 1:00 a.m. near the Route 30 Bypass in West Whiteland Township.
Authorities say the driver - identified as 25-year-old Meghan McGuire from Berwyn - was killed.
The view from Chopper 6 HD showed a box truck with damage to its side. A heavily damaged Volkswagen Passat was also on the scene.
The passenger in the vehicle - 55-year-old Richard Laub III - was hospitalized for non-life-threatening injuries and has since been released.
Police are still investigating the exact cause of the crash. On Friday, the southbound lanes of the highway were closed between the bypass and Boot Road for more than eight hours.
Police ask anyone with information to call (610) 363-0200 or (610) 692-5100.