Nonmelanoma skin cancer is the most frequently diagnosed malignancy in the United States, and multiple exposures to solar ultraviolet (UV) radiation (particularly its UV-B component, 290–320 nm) is its major cause. “Chemoprevention” by naturally occurring agents is being appreciated as a newer dimension in the management of neoplasia including skin cancer. We recently demonstrated that resveratrol (trans-3,5,4-trihydroxystilbene), an antioxidant found in grapes, red wines and a variety of nuts and berries, imparts protection from acute UV-B–mediated cutaneous damages in SKH-1 hairless mice. Understanding the mechanism of resveratrol-mediated protection of UV responses is important. We earlier demonstrated that resveratrol imparts chemopreventive effects against multiple UV-exposure–mediated modulations in (1) cki-cyclin-cdk network and (2) mitogen activated protein kinase (MAPK)-pathway. This study was conducted to assess the involvement of inhibitor of apoptosis protein family protein Survivin during resveratrol-mediated protection from multiple exposures of UV-B (180 mJ/cm²; on alternate days; for a total of seven exposures) radiations in the SKH-1 hairless mouse skin. Our data demonstrated that topical pretreatment of resveratrol (10 μmol in 200 μL acetone/mouse) resulted in significant inhibition of UV-B exposure–mediated increases in (1) cellular proliferations (Ki-67 immunostaining), (2) protein levels of epidermal cyclooxygenase-2 and ornithine decarboxylase, established markers of tumor promotion, (3) protein and messenger RNA levels of Survivin, and (4) phosphorylation of survivin in the skin of SKH-1 hairless mouse. Resveratrol pretreatment also resulted in (1) reversal of UV-B–mediated decrease of Smac/DIABLO and (2) enhancement of UV-B–mediated induction of apoptosis, in mouse skin. Taken together, our study suggested that resveratrol imparts chemopreventive effects against UV-B exposure–mediated damages in SKH-1 hairless mouse skin via inhibiting Survivin and the associated events.