The administration of fisetin (250 and 500 nmol) in SKH‐1 hairless mouse provides protection against solar ultraviolet B (UVB) radiation skin cancer through multiple pathways such as reduction in hyperplasia and PGE2; infiltration of inflammatory cells, receptors (EP1‐EP4), COX‐2, and MPO activity; and reduction in inflammatory cytokines (TNF‐α, IL‐1β, and IL‐6) and cell proliferation markers. The gene discussed is PTGER4; the disease is skin neoplasm.