RNA interference using small interfering RNA (siRNA) is an effective means of silencing gene expression in cells. Intradermal administration of nucleic acids via gene gun represents an efficient method for delivering nucleic acids to professional antigen-presenting cells in vivo. In this study, we show that the coadministration of DNA vaccines encoding human papillomavirus type 16 E7 with siRNA targeting key proapoptotic proteins Bak and Bax prolongs the lives of antigen-expressing dendritic cells in the draining lymph nodes, enhances antigen-specific CD8⁺ T-cell responses, and elicits potent antitumor effects against an E7-expressing tumor model in vaccinated mice. Our data indicate that intradermal administration of siRNA to manipulate gene expression represents a plausible strategy for modification of the properties of professional antigen-presenting cells in vivo to enhance cancer vaccine potency.