Abstract: Objective To study the effects of mutant p27 (p27 mt) gene on invasive growth of SMMC-7721 (HCC) in nude mice. Methods A mouse model of human hepatocellular carcinoma (SMMC-7721) was established by subcutaneous transplantation in BALB/c mice. The PBS(100μl), adenovirus-mediated mutant p27 (Ad-p27mt，5.0×109 pfu, 100μl) and Lac-Z (Ad-Lac-Z，5.0×109 pfu, 100μl) were injected into the transplanted tumors. Subsequently, the tumor size was tested in every 3 days. The expression of p27 protein, CD44v6 and Ⅷ factor in the transplanted tumors were detected through immunofluorescence method and Semi-quantitative analysis of the expression of P27 protein, CD44v6 and Ⅷ factor were evaluated by integral optical density (IOD) and average optical density (AOD) through Image-Pro Plus software. Results Compared with the Ad-Lac-Z and blank control group, P27 protein expression in Ad-p27 group was obviously increased (P<0.01), and the expression of CD44v6 and Ⅷ factor were significantly decreased (P<0.05). Conclusion Over-expressing p27 mt could significantly inhibit the growth of SMMC-7721 in nude mice through angiogenesis inhibition, and obviously decreased the invasive ability of SMMC-7721 through CD44v6 expression down-regulation.