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Objectives: Although many pathways have been studied using pure ultraviolet A (UVA) or ultraviolet B (UVB) irradiation, the signaling pathways induced by SUV (i.e., sunlight) are not understood well enough to permit improvements for prevention, prognosis, and treatment.The role of cellular signal transduction pathways activation by solar ultraviolet (SUV) irradiation in skin tumorigenesis is not fully investigated.Here, we aimed at determining the dominant signaling pathway involved in SUV irradiation and its role in skin carcinogenesis.Methods: The Parallel protein kinase array and Western blotting was used to investigate the dominant signaling pathway involved in SUV irradiation.P38 α conditional knockout mice and Immunohistology were used to investigate the role of P38 α in Solar UV induced skin carcinogenesis.Results: Our results indicated that the p38-related signal transduction pathway was dramatically affected by SUV irradiation.SUV (60 kJ UVA/m2/3.6 kJ UVB/m2) irradiation stimulates phosphorylation of p38a (MAPK14) by 5.78-fold, MSK2 (RPS6KA4) by 6.38-fold, and HSP27 (HSPB1) by 34.56-fold compared with untreated controls.By investigating the tumorigenic role of SUV-induced signal transduction in wild-type and p38 dominant-negative (p38 DN) mice, we found that p38 blockade yielded fewer and smaller tumors.Conclusion: These results establish that p38 signaling is strongly activated and critical for SUV-induced skin carcinogenesis.