AIM: To study the effect of adenovirus (Ad)-p53 gene therapy on hepatocellular carcinoma (HCC) in a rabbit model.METHODS: VX2 tumor was grown in the liver of 24rabbits. Animals were divided into four groups: group A receiving trans-arterial gene therapy (Ad-p53) only,group B receiving combined Ad-p53 therapy and transarterial embolization (lipiodol), group C receiving transarterial chemoembolization (lipiodol + mitomycin C),control group (D) receiving sodium chloride. Tumor volume (V1) was measured by using MRI (d 13).Interventional procedure was applied (d 14).Tumor volume (V2) was assessed by MRT (d 21) and the mean ratio (V2/V1) was calculated. After the second MRI,specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 antibody.The positive expression was scored.RESULTS: Compared with control group ((-x) = 3.14± 0.64), therapeutic groups all showed a significant decrease in the tumor growth ratio (P ＜ 0.05). A slight difference was found between group A ((-x) =2.35 ±0.59) and group B ((-x) = 1.75 ± 0.28) (P = 0.048). Nostatistically significant difference was observed between group B and group C ((-x) = 2.00 ± 0.44). The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C (P ＜ 0.05).Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them.CONCLUSION: Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.