According to the Advocate, the fatal crash occurred near the 63 mile marker on Interstate 10, just past the 4.4-mile bridge over the Pascagoula River.
The four people who died in the crash were all occupants of a Ford Expedition.
In addition to the SUV and two 18-wheelers, the crash also involved a red Nissan and two pickups, one pulling a camper. The driver of one of the pickups has been hospitalized.
Crews are working to clear the scene and the crash remains under investigation.