The crash occurred at exit 57 around 4:00 p.m.
"The closure affects all southbound lanes from exit 52: US 11/I-76 Turnpike-Middlesex to exit 57: PA 114-Mechanicsburg," says PennDOT.
The PA Turnpike Commission has not commented.
At least two vehicles are involved.
Initial reports on the emergency radio scanners state that at least one person was airlifted from the scene and there are two victims, but dispatch has not confirmed this at the time of publishing.
The corner has not been called to the scene.
The highway is backed up for several miles slowing down traffic for at least four exits in the southbound lanes.
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