Objective To investigate the action mechanism of an anti-photosensitivity mixture on skin photodamage. Methods Twenty-eight BLAB/c mice were divided into 4 groups, i.e., normal control group,treatment group, negative and positive control groups; the last three groups were irradiated with a single dose of UVB at 300 mJ/cm2 after 7-day pretreatment with sodium chloride physiological solution, anti-photosensitivity mixture, and hydroxychloroquine, respectively. Twenty-four hours after the irradiation, mice were killed and skin tissue samples were obtained at the irradiated sites. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and immunohistochemical staining were carried out to detect cell apoptosis,Fas and Caspase-3 protein expressions respectively. Results An increase was observed in the expression level of Fas and Caspase-3 and in the apoptotic index in keratinocytes from UV-irradiated mice compared with unirradiated control mice (all P ＜ 0.01 ). In comparison with sodium chloride physiological solution, the antiphotosensitivity mixture suppressed the UV irradiation-induced increase in the expression intensity of Fas and Caspase-3 and apoptotic index in keratinocytes (P ＜ 0.05 or 0.01 ). Conclusions The anti-photosensitivity mixture could alleviate UV-induced inflammatory damage to and apoptosis in epidermal keratinocytes, likely by regulating cell apoptosis and Caspase-3 pathway.