The aging of skin, including sunburning, is caused by ultraviolet (UV) irradiation. Here, we examined the inhibitory effect of ascorbic acid (AsA) and its derivatives AsA 2-phosphate (AA-2P) and AsA 2-glucoside (AA-2G) on UV-B– induced cytotoxicity in HaCaT keratinocytes. Results show that cell viability significantly decreased when exposed to UV-B at 0.1–0.4 J/cm² in a dose-dependent manner. In this study, AsA could not inhibit cytotoxicity, but AA-2P and AA-2G was able to cancel the harmful effect of UV-B when treated at high levels of 0.5–5 mM. These results indicate that the masking of the C-2 OH group may be an effective modification for AsA to inhibit UV-B–induced cytotoxicity in human keratinocytes.