Objective To investigate the therapeutic efficacy of compound immunotherapy of tumor-derived heat shock protein 70 (HSP70) and interleukin-2 (IL-2) on tumor-bearing mice, and to provide reference for translating this strategy to human cancer. Methods Cell culture, techniques for protein extraction and purification, SDS-PAGE, Wes t blot and capillary electrophoresis for HSP70 detection and purity analysis, and animal experiments were used. Mice were treated with HSP70 5 or 10 μg and IL-2 50 kU, 100 kU or 2 kU (maintaining dosage) at pre viously designated intervals. Results Both the mono-administration of either HSP70 or IL-2 and the compound immunoth erapy of HSP70 and IL-2 obviously inhibited the growth of the implanted tumor and prolonged the life span of the mice to different extents. However, long periods of tumor-free suvival (over 90 days) were demonstrated only in HSP70 10 μg group, HSP70 10 μg-IL-2 50 kU group, and HSP70 10 μg-IL-2 100 kU group (4 0%, 40%, 60% respectively). On the other hand, none of the mice in the rest gr oups achieved long-term survival. Statistical significance was apparent in com parison with the groups without long period survival (P<0.025-0.05). Conclusion Our research revealed that tumor-derived HSP70 immunotherapy was much more effective than IL-2 alone. And in compound immunotherapy, HSP70 was the main factor in delaying or eradicating the tumors. The proper combination of HSP70 and IL-2 (10 μg HSP70 and 100 kU IL-2 in this experimental mouse model) clea rly enhanced the immunotherapy efficacy which indicated that the specific immuno therapy as a main part of tumor immunotherapy assisted by cytokine immunotherapy would be a promising strategy in cancer treatment.