In this study, the inhibitory effect of transmembrane PBLs on HepG2 hepatocarcinoma and the potential application of PBLs on immune system of KM mice loaded with HepG2 hepatocarcinoma were carefully investigated and discussed. The animal model was established via inoculation of HepG2 hepatocarcinoma cells at the hind thigh of KM mice. Recombinant vector plasmids were transfected at the same site for gene therapy by injection to observe the inhibitory effect of PBLs on growth of tumor. A panel of genes such as IL-2, IFN-γ and HSP70 from tumor tissues at various time intervals were analyzed by RT-PCR. Flow cytometry was used to evaluate the proliferation and cytotoxicity of splenocytes after PBLs transfection. Synergistic effect of PBLs with HSP70 was also studied. It was found that the growth of tumor was significantly suppressed after the transfection of PBLs. Under the conditions of presence of PBLs, the proliferations of splenocytes and cytolysis in early phase of tumor development were significantly enhanced, and this antitumor effect was further improved by the synergistic effect of PBLs with HSP70. Therefore, the membrane-type PBLs might behave as an effective immunoregulator to enhance antitumor immune responses and the antitumor immunity is improved by the combined effect of PBLs and HSP70.