Hepatocellular carcinoma (HCC) is an aggressive and rapidly fatal malignancy representing the common cancer worldwide. The specific cellular gene involved in carcinogenesis has not been fully identified. The ubiquitin-like modifier FAT10, a recently reported to be over-expressed in 90% of hepatocellular carcinoma (HCC) carcinomas, and might be regarded as an ideal target for HCC therapy. In the present study, we utilized DCs transduced with FAT10 recombinant adenovirus to elicit CTLs in vitro. In addition, the Trimera mice were immunized with the transduced DCs to elicit the immune response in vivo. The results demonstrated that transduced DCs could effectively induce specific CTL response against HCC without lysing autologous lymphocytes, but also significantly inhibit the tumor growth and prolong the life span of tumor bearing mice. These results suggest that FAT10 recombinant adenovirus transduced DCs might be a promising therapeutical strategy for treatment of HCC.