Pennsylvania Route 378 (PA 378) is a north-to-south road in Lehigh and Northampton counties in the Lehigh Valley region of the U.S. state of Pennsylvania. The southern terminus is at PA 309 in Center Valley. Its northern terminus is at U.S. Route 22 (US 22) in Bethlehem. The route heads north from PA 309 as a two-lane undivided road through Upper Saucon Township and Lower Saucon Township before crossing South Mountain into Bethlehem. Here, PA 378 follows city streets through Bethlehem's South Side, intersecting the northern terminus of PA 412. The route becomes a four-lane freeway and crosses the Lehigh River before continuing north to US 22. PA 378 is the only highway from US 22 to Center City Bethlehem, and a quick route for visitors traveling to the Wind Creek Bethlehem casino resort on the city's South Side.

Northampton County is a county in the Commonwealth of Pennsylvania, United States. As of the 2020 census, the population was 312,951. Its county seat is Easton. The county was formed in 1752 from parts of Bucks County. Its namesake was the county of Northamptonshire in England, and the county seat of Easton was named for Easton Neston, a country house in Northamptonshire. The county is part of the Southeast Pennsylvania region of the state.