South Carolina Highway 181 (SC 181) is a 6.430-mile-long (10.348 km) state highway in the U.S. state of South Carolina.

The highway connects the Georgia state line with Starr.

SC 181 begins at the Georgia state line at a point southwest of Starr, within Anderson County, where the roadway crosses over the Savannah River and continues as Georgia State Route 181 (Smith-McGee Highway).

The highway continues to the northeast and enters Starr.

There, it meets its northern terminus, an intersection with SC 412 (Rainey Road/Stones Throw Avenue).