South Carolina Highway 154 (SC 154) is a 16.680-mile-long (26.844 km) state highway in the U.S. state of South Carolina.

SC 154 begins at an intersection with U.S. Route 76 (US 76; Florence Highway) in Mayesville, within Sumter County, where the roadway continues as Mayes Open Road.

It travels to the north-northwest and enters Lee County.

The highway passes Lower Lee Elementary School and goes through rural areas of the county.

A short distance later, it enters Bishopville, where it meets its northern terminus, an intersection with US 15 (Sumter Highway).