U.S. Route 78 (US 78) is a 142.207-mile (228.860 km) U.S. highway that travels from Swifton, Arkansas to Charleston, South Carolina.

In the U.S. state of South Carolina, it travels from the Savannah River at North Augusta to its eastern terminus in Charleston; connecting the cities of Aiken, Summerville, and North Charleston.

[7] Traveling in a southeasterly direction, it goes through the cities and towns of Williston, Blackville, Denmark, Bamberg, Branchville and St. George, where connects with I-95.

Continuing east, it passes through Dorchester and begins to parallel with I-26 in a southeasterly direction through Summerville.

By 1967, US 78 was adjusted to bypass south of mainstreet Blackville, leaving a secondary road, but was later upgraded as a connector (signed as a business loop).