Objective: In this study, we investigated whether morin, a natural flavonoid, could able to inhibit ultraviolet B (UVB)-induced carcinogenesis in the skin of Swiss albino mice. Methods: The mice were exposed to UVB radiation (180 mJ/cm2) on weekly thrice for 30 weeks, and morin was administered intraperitoneal and topical application 1 h before UVB exposure. UVB radiation induces the overexpression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and Bcl-2 genes. Results: Morin significantly prevented UVB-induced activation of COX-2, iNOS, VEGF, TGF-β, and Bcl-2 expression in mouse skin. Thrombospondin-1 (TSP), a novel endogenous factor, inhibits angiogenesis and inflammation. Conclusion: The present study illustrates that the protective effect of morin against UVB-induced carcinogenesis may be modulated through activation of TSP-1 in UVB-exposed Swiss albino mice. © 2018 Elsevier B.V., All rights reserved.