Ultraviolet radiation (UVR) is the major cause of numerous skin diseases, including sunburn, skin aging, and skin cancers. Pyruvate is a key intermediate in cellular metabolic pathways, which has shown protective effects against oxidative stress and apoptosis, but its role in UV protection remains unclear. Here we established human and mice in vivo model and found that pyruvate protects both human and mouse skin from UVB-induced DNA damage. Moreover, assays in primary keratinocytes and melanocytes further supported the protective role of exogenous pyruvate against UVB-induced DNA damage. Mechanically, pyruvate stimulates the activation of Histone H3 Lysine 9 (H3K9) acetylation, which is an essential step for nucleotide excision repair (NER) pathway. In conclusion, our results suggest that treatment of pyruvate might be an effective strategy to prevent UVB-induced skin diseases.