| State: | SC |
| Type: | SC |
| Route: | 181 |
| Map: | SC 181 map.svg |
| Alternate Name: | Smith–McGee Road |
| Length Mi: | 6.430 |
| Length Ref: | [1] |
| Established: | 1942 |
| Direction A: | South |
| Terminus A: | at the Georgia line near Starr |
| Direction B: | North |
| Terminus B: | in Starr |
| Counties: | Anderson |
| Previous Type: | SC |
| Previous Route: | 179 |
| Next Type: | SC |
| Next Route: | 182 |
South Carolina Highway 181 (SC 181) is a 6.43adj=midNaNadj=mid 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). It travels to the northeast and has a brief concurrency with SC 187. 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). Here, the roadway continues as Smith-McGee Road.