| Country: | JPN |
| Type: | National |
| Route: | 221 |
| Map Custom: | yes |
| Length Km: | 74.6 |
| Length Ref: | [1] |
| Established: | 18 May 1953 |
| Direction A: | North |
| Terminus A: | in Hitoyoshi |
| Direction B: | South |
| Terminus B: | in Miyakonojō |
| Previous Type: | Route |
| Previous Route: | 220 |
| Next Type: | Route |
| Next Route: | 222 |
National Route 221 is a national highway of Japan connecting Hitoyoshi and Miyakonojō in Japan, with a total length of 74.6km (46.4miles).