Abstract Increasing knowledge demonstrate that prostate stem cell antigen (PSCA) is a promising candidate for immunotherapy of advanced prostate cancer. However, tumor escape with down-regulation of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T-cell responses against several immunodominant antigens may circumvent this potential drawback. In this study, we prepared the chaperone complex vaccine based on PSCA and GRP170, and utilized it to immunize the C57BL/6 mice. In addition, the T-cell response was monitored with ELISPOT and 51Cr-release assays, and the tumor growth and the life span of tumor-bearing mice were assessed. The results demonstrated the chaperone complex based on PSCA and GRP170 could enhance the T-cell mediate immune responses, which significantly inhibited the tumor growth and prolonged the life span of tumor-bearing mice. In conclusion, our findings supported the strategy of chaperone complex, based on PSCA and GRP170, could be an effective treatment for prostate cancer therapy.