Aim: Allogeneic bone-marrow transplantation (BMT) can induce a powerful graft-versus-tumor (GVT) effect on not only hematologic malignancies but also on solid tumors. However, graft-versus-host disease (GVHD) is a major complication of allogeneic BMT. We assessed GVT effect on hepatocellular carcinoma (HCC) and the effects of hepatocyte growth factor (HGF) gene transduction on GVHD in HCC transplanted mice. Methods: (C57BL/6 x C3H/HeJ)F₁(B6C3F1, H-2^bxk) mice were used as recipients and C3H/HeJ(H-2^k) mice were used as donors. Hepa-1a (a C57L mouse derived hepatoma cell, H-2^b) was subcutaneously injected into the recipient mice. Tumor bearing mice were treated in the following ways: Group 1, no treatment; Group 2, total body irradiation (TBI); Group 3, TBI and BMT; Group 4, TBI and BMT with empty vector; Group 5, TBI and BMT with HGF gene transduction, Group 6, TBI and BMT with FK506, a representative immunosuppressive agent, administration. Acute GVHD was assessed by histological examination of the liver, small intestines and large intestines. Results: Tumor growth was markedly suppressed in mice that were received an allogeneic BMT. Donor derived CD8⁺ T cells had infiltrated into the tumor, and cytotoxic CD8⁺ T cells against HCC were present. However, among the four groups that received a BMT, this suppressive effect was weaker in Group 6 compared to the other three groups (Group 3, 4 and 5). HGF gene transduction improved GVHD while preserving the GVT effects. Conclusion: Allogeneic BMT markedly suppresses the growth of HCC. Simultaneous HGF gene transfer can suppress GVHD, while preserving the GVT effect.