As a regulator of Tregs and inflammation, the transcription factor forkhead/winged helix transcription factor 3 (FOXP3) plays important roles in some types of dermatitis. However, the detailed mechanism of FOXP3 has not been well defined. Increasing evidence indicates that FOXP3 involves epigenetic mechanisms to fulfill its functions. We anticipated several types of mechanisms that might link FOXP3 to the epigenetic profile, and assessed the impact of FOXP3 on the global profile of histone H3 acetylation and methylation. We found that overexpression of FOXP3 increased histone H3-lysine9 demethylation (H3K9me2), H3K79me2, H3-lysine9 acetylation (H3K9ac), and H3K18ac. When cells were exposed to ultraviolet (UV) light, FOXP3 clearly increased the levels of H3K9ac and H3K18ac. Hypoxia increased H3 modifications, whereas the overexpression of FOXP3 during hypoxia stabilized H3K9me2, H3K79me2, H3K9ac, and H3K18ac levels almost back to normal. FOXP3 functions opposite to TRAF6 (TNF receptor-associated factor 6) in H3 modifications. The modifications altered by FOXP3 may influence the cell cycle and apoptosis; we showed that FOXP3 increased the proportion of cells in S phase, decreased the proportion of cells in G2/M phase, and markedly enhanced cell apoptosis. In conclusion, this work provides evidence that FOXP3 is an epigenetic regulator, and implies a new molecular basis for the pathogenesis in some diseases.