One of the most significant risk factors associated with the development of skin disease is exposure to UVB radiation from the sun. In particular, UVB light can activate inflammatory and apoptotic pathways, leading to skin damage. Anthocyanins, a group of flavonoids present in many common vegetable foods, are known for their chemopreventive activity. The aim of this study was to evaluate the efficacy of cyanidin-3-O-glucoside (C3G) on modulation of cellular responses following exposure to UVB doses in human keratinocytes (HaCaT). In our study, UVB-exposed cells showed significant increase of the translocation of transcription factors NF-kB and AP-1, overexpression of the proinflammatory cytokine IL-8, cleavage of procaspase-3 (a key step in apoptotic pathway), and DNA fragmentation. All these effects elicited by UVB exposure were clearly inhibited by pretreating HaCaT cells with C3G. In conclusion, our data demonstrate that C3G can protect skin cells against the adverse effects of UVB radiation and suggest that it might successfully be employed as a skin photoprotective agent.