A self-enhancing humor style (SEHS) plays an important role in the regulation of negative emotion through humorous perspective-taking. Following the mind-reading theories of humor, we investigated the relationship between gray-matter volume (GMV) of brain areas related to theory of mind and SEHS in young college students, using voxel-based morphometry analysis. We then performed a voxel-wise analysis of covariance to assess any moderation effect of cognitive empathy on the relationship. Results demonstrated that higher SEHS scores were associated with larger GMV of the precuneus in the group with high cognitive empathy, but there was no association in the group with low cognitive empathy. These results suggest that high cognitive empathy and increased precuneus volume can predict greater use of self-enhancing humor in young healthy individuals.