Squamous cell carcinoma (SCC) is one of the commonest dermatological malignancies. Resveratrol (Res) is one type of polyphenolic compound which was first identified from the roots of Veratrum grandinorum in 1940. The previous studies found that Res can promote apoptosis of a variety of tumor cell, especially SCC cells. However it is rare to study the inhibition mechanism of Res in the animal model. In this study, through the establishment of human cutaneous SCC A431 xenografts in nude mice, we observed Res inhibition effect and investigated the inhibition mechanism by checking the expression of apoptosis-related factors, p53, ERK and survivin. The results showed that the xenograft volume and weight of Res groups were less than those of the control groups (P<0.05), but the net body mass of nude mice of Res groups was not significantly different from the control groups (P>0.05). The apoptotic index of Res groups were significantly higher than the control groups (P<0.05). The protein and mRNA expression of p53 and ERK were statistically positively correlated (P<0.05) and significantly increased in Res high- and medium-dose groups compared with the control groups (P<0.05). Moreover, the protein and mRNA expression of SVV were negatively correlated with p53 (P<0.05) and lower than the control groups (P<0.05). The results demonstrate Res inhibitory effect and indicate that the inhibition mechanism of Res is to upgrade the protein and mRNA expression of p53 and to downgrade the protein and mRNA expression of SVV, thus inducing the apoptosis of tumor cells.