In a cirrhotic liver, the regenerative ability and specific functions are impaired; a hepatic resection increases the possibility of postoperative liver failure. Hepatocyte growth factor (HGF) stimulates liver regeneration, accelerates restoration of hepatic function, and improves fibrosis. A truncated type II transforming growth factor-β receptor (TβTR), which specifically inhibits TGF-β signaling as a dominant-negative receptor, appears to prevent the progression of liver fibrosis. We demonstrated the therapeutic efficacy of adenovirus-mediated HGF and TβTR gene transduction after partial hepatectomy for liver cirrhosis. Rats were treated with dimethylnitrosamine for 3 weeks, and they all had severe cirrhosis. After partial hepatectomy (10%), we injected adenovirus expressing bacterial β-galactosidase (AdLacZ), adenovirus expressing a truncated type II TGF-β receptor (AdTβTR), adenovirus expressing hepatocyte growth factor (AdHGF), or AdTβTR + AdHGF into the portal vein, which was followed by an additional 2-week dimethylnitrosamine treatment. On histologic examination, fibrotic tissue had decreased in the livers of the AdTβTR + AdHGF–treated rats compared with rats that were treated by AdLacZ, AdTβTR alone, and AdHGF alone. Liver function, which included serum levels of alanine aminotransferase, improved significantly in AdTβTR + AdHGF–treated rats compared with all other groups. The number of hepatocytes that were positive for proliferating-cell nuclear antigen was greater (P < .05) in AdHGF alone and AdTβTR + AdHGF–treated rat livers than in AdLacZ- and AdTβTR-treated rats. All AdTβTR + AdHGF–treated rats survived >60 days, and AdTβTR + AdHGF treatment markedly improved the survival rate after a partial hepatectomy. Our results suggest that the combination of HGF and TβTR gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration.