Introduction: Vaccinology provides promising approaches for the control of various infectious diseases. Among different strategies, DNA vaccines offer attractive research opportunities for development of vaccines for induction of antigen-specific immunity owing to their stability, simplicity of delivery, safety and cost effectiveness. However, there is a need to increase their potency by the use of adjuvants such as glycoprotein 96 and electroporation delivery. On the other hand, the attenuated or non-pathogenic live vectors have been used to deliver DNA into cells as efficient delivery tools in gene therapy. Recently, a non-pathogenic protozoan, Leishmania tarentolae (L. tar), has attracted attention as an in situ protein-delivery vehicle. Cervical cancer is the second largest cause of cancer deaths among women worldwide and human papillomaviruses (HPV) is reportedly a frequent cause of this type of cancer. Methods: In the current study, we compared the potential of live L. tar-based and DNA-based vaccines expressing HPV16 E7 linked to C-terminal fragment of gp96 in a tumor mouse model. Results: We found that subcutaneous DNA injection with E7-CT (gp96), followed by electroporation, generate a significant E7-specific IFN-γ immune response and in vivo protective effects compared to transgenic L. tar-E7-CT (gp96) in challenge experiments with TC-1. Conclusion: It could be concluded that the DNA vaccine showed higher efficacy compared to the non-pathogenic live parasite-based vaccine in the tumor mice model. Vac Res , 2014, 1 (1): 22-25