The crash happened around 6:45 p.m. near mm 4 along I-81 southbound in Franklin County.
The interstate was shut down along the southbound side from Exit 5 to the US 11 Exit.
Trooper Hicks with Pennsylvania State Police said the accident involved two vehicles, and one flipped over onto the interstate.
The six people were transported to Meritus Medical Center for treatment.
Both cars have been towed from the scene and both lanes were reopened at 8 p.m.
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