Background: Vaccines based on virus-like particles are effective against Human Papilloma Virus (HPV) infection; however, they have not shown a therapeutic effect against HPV-associated diseases. New immunotherapy strategies based on immune responses against tumor antigens can positively affect the clearance of HPV-associated lesions. Objective: To generate two therapeutic fusion DNA vaccines (optimizedE7/mouseHSP70 and wildE7/mouseHSP70) to induce antitumor specific responses in mice models. Methods: Mice were immunized with recombinant DNA vaccines. The splenocytes of immunized mice were collected and lactate dehydrogenase and IFN-γ productions were measured after three injections in order to evaluate cytotoxic T lymphocytes (CTLs) activity. MTT assay was carried out for lymphocyte stimulation. Results: The fusion DNA vaccines, specifically uE7-HSP70, elicited varying levels of IFN-γ and CTLs responses compared to the control group (P<0.05). Furthermore, antitumor response and tumor size reduction in fusion DNA vaccines groups were significantly higher than in the negative control group (P<0.05). Conclusion: It is concluded that our fusion DNA vaccines considerably enhanced specific cellular responses against HPV tumor model. In addition, optimized E7 showed a notable immunogenicity and inhibitory effect on the reduction of tumor size.