Abstract： Objective To evaluate the efficacy of recombinant adenovirus- P53 (rAd- P53) transcatheter hepatic arterial chemoembolization (TACE) plus traditional Chinese medicine in treatment of primary hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods Between January 2007 and August 2010, 78 patients with HCC and PVTT registered to our hospital were recruited in this study. The patients were divided into a control group (n=35) to receive TACE using pirarubicin (THP,20～40 mg), mitomycin (MMC, 10 mg), carboplatin (CBP, 100～300 mg) and mixed lipiodol ( 10～20 ml),and a treatment group (n=43) to receive TACE using the same agents as in control group combined with rAdP53 injection ( 1 × 1012～4× 1012 virus particle). During the perioperative period, traditional Chinese medicine were given to the treatment group. The treatments for all patients were delivered monthly for consecutively three months. Changes from baseline in size of primary tumor and PVTT, complete blood counts, liver function, level of alpha fetoprotein (AFP) , and quality of life as measured by Karnofsky score were compared between the two groups. Results Reduction in sizes of the primary tumor and PVTT was found in the control and treatment groups after operation. The effective rates were respectively in 79.1% and 76.7% of patients in treatment vs 42.9% and 40.0% in the control group, with significant differences (all P＜0.05).Leucopenia occurred in 25.6% (including 18.6% with grade Ⅰ , 4.7% with grade Ⅱ , 2.3% with grade Ⅲ and 0% with grade Ⅳ leucopenia) of the patients in the treatment group, compared significantly with 80.0%(including 11.4% with grade Ⅰ , 28.6% with grade Ⅱ , 34.3% with grade Ⅲ and 5.7% with grade Ⅳleucopenia) of patients in control group. There were statistical significance in rate and degree of decline between two groups (all P＜0.05 ). Compared with control group, the patients in treatment group showed better liver function (79.1% vs 37.1% with Child-Pugh A, 16.3% vs 31.4% with Child-Pugh B, and 4.7% vs 31.4%with Child-Pugh C, P=0.000) , higher Karnofsky scores (72.1% vs 42.9%, P=0.009) and lower AFP (74.4% vs 40.0%, not statistically significant, P=0.912). Conclusion rAd-P53 injection combined with TACE and traditional Chinese medicine was shown to have improve the therapeutic efficacy, reduce adverse reactions and increase quality of life in patients with hepatocellular carcinoma and portal vein tumor thrombus.