Our previous studies have shown that ginsenoside Rg2 protects the genotoxicity of UVB via earlier upregulation of p53 and GADD45 proteins. In the present study, we investigated the effects of Rg2 on the genotoxicity of UVB in cells transfected with p53 siRNA. The cells transfected with control siRNA, exposed to UVB and then post-incubated with 100 μM Rg2 showed increase in cell viability to about 20%, as compared to no significant increase in cell viability in cells transfected with p53 siRNA. The UVB-induced apoptosis was also decreased by 100 μM Rg2 to about 30% in control siRNA-transfected cells, as compared to only 10% decrease in the apoptosis in p53 siRNA-transfected cells. The p53 and GADD45 protein levels in control siRNA-transfected cells after UVB exposure increased to about 3.5 and 2.7 fold, respectively, as compared to the nontreated control. The increased p53 and GADD45 protein levels were downregulated by Rg2 in an Rg2 concentration-dependent manner. However, the protective effects of Rg2 were not shown in p53 siRNA-transfected cells. All these results suggest that Rg2 protects cells against UVB-induced genotoxicity by increasing DNA repair, in possible association with modulation of protein levels involved in p53 signaling pathway. ARTICLE HISTORY