The accident happened around 8:00 a.m. in the westbound lanes of I-78 at the Pennsylvania state line in Williams Township.
Police say the driver of a car had stopped to pay a toll when a tractor-trailer came through the booth and hit the car, pushing it off to the side.
Both vehicles then caught fire.
Emergency crews say at least one person is dead. But they still can't reach the car, so they're not sure if anyone else was inside.
The driver of the truck was uninjured.
Police closed I-78 on the New Jersey side starting at Exit 3 while conducting their investigation.