The injection of naked plasmid DNA directly into the muscle cells of hosts has been shown to induce potent immune responses, as well as to express large amounts of gene product; this has provided a new way of treatment for tumor. The past ten years have witnessed tremendous growth in the field of gene therapy for cancer using intramuscular injection of plasmid DNA. Many studies have suggested that the immunostimulatory DNA sequences(ISS) in vector backbone of plasmid DNA, delivering adjuvant and mitogenic activity, are necessary for effective intradermal gene immunization. It has been postulated that muscle cells serve as a reservoir of expressed antigen with subsequent transfer to bone marrow-derived APCs. Thus, immunization with plasmid DNA can trigger strong and persistent cell-mediated and humoral immune responses to the antigen encoded by the plasmid. Increasing evidence demonstrates that DNA immunization can prevent or inhibit tumor development. In this review, the present authors presented a discussion on the characteristics of immune response to DNA vaccines and a summary of the effects of immune response against tumors.