BACKGROUND It has been reported that the tumor suppressor gene, PTEN, which is inactivated in many malignant tumors, plays an important role in apoptosis, cell cycle arrest, cell migration, and cell spread. For cancer gene therapy, one of the most important problems is low gene transfection efficiency. METHODS In the present study, to take full advantage of adenovirus in gene expression, we prepared mannan-modified recombinant adenovirus using the PTEN gene (Man-Ad5-PTEN) and investigated the effect of Man-Ad5-PTEN combined with docetaxel (Man-Ad5-PTEN-docetaxel) on tumor growth in a murine model of hepatocellular carcinoma. RESULTS Man-Ad5-PTEN effectively suppressed tumor growth and induced significant apoptosis of murine H22 hepatoma in vivo. Apoptosis levels in tumor-bearing mice treated with Man-Ad5-PTEN-docetaxel were significantly higher than those in tumor-bearing mice treated with naked Ad5-PTEN, Man-Ad5-PTEN, or docetaxel alone. Treatment with Man-Ad5-PTEN-docetaxel resulted in a significant inhibitory effect in this tumor model. Compared with the controls treated with phosphate-buffered solution, the tumor inhibition rate with naked Ad5-PTEN, docetaxel, Man-Ad5-PTEN, and Man-Ad5-PTEN-docetaxel was 48.69%, 49.98%, 75.88%, and 96.93%, respectively. CONCLUSION These results suggest that combined treatment with Man-Ad5-PTEN and other chemotherapeutic agents may be a potent adjuvant therapeutic approach for the treatment of hepatocellular carcinoma.