e15024 Background: Treatment options for advanced hepatocellular carcinoma (HCC) are limited due to patients’ poor condition, and resistance to both chemo- and radio-therapy. Trans-catheter embolization (TAE) or Trans-catheter chemo-embolization (TACE) is the most widely used locoregional treatment for advanced HCC. But no solid evidences support the beneficial effect of the chemotherapy in TACE. Many advanced HCC patients also can’t tolerate the locoregional chemotherapy. The p53 gene has multiple anticancer functions and does not have any of the immune-inhibitory effects of chemo- or radio-therapy. The objectives of this study are to investigate TAE plus recombinant adenoviral human p53 gene (rAd-p53) in treatment of advanced HCC. Methods: Fifty-eight patients with advanced, unresectable HCC were randomly to two groups: TAE plus p53 group (TAE-p53G), or TAE group (TAEG). The study patients included 56 males and 2 females with an average age of 62.5 (53-89) years old and with Child-Pugh score A or B (42 or 16, respectively). The patients received 3 times of TAE plus rAd-p53 for TAE-p53G or TAE only for TAEG, once in a month for 3 months. The TAE materials consist of gelatin sponge particles (GSP) alone or plus 2-4 x 1012viral particles of rAd-p53, mixed into 30 ml suspension. The study endpoints included response rate, one-year survival, liver function, and adverse effects. Results: After 3-5 days of the first treatment, CT scan showed deceased tumor density in all the study cases. At 6 months after the first treatment, based on the RECIST standard, 31.0% (9/29) and 51.7% (15/29) patients in TAE-p53G achieved a complete response (CR) and partial response (PR), respectively, versus 17.2% (5/29) and 37.9% (11/29) of CR and PR in TAEG, respectively. One-year survival rates were 79.4% and 60.7% with median survival time of 11.7 and 8.3 months for TAE-p53G and TAEG, respectively. There are no significant changes of liver functions in both groups after treatment. Mild or median fever was observed in all the patients in TAE-p53G. No serious adverse events or complications observed. Conclusions: TAE using GSPs plus rAd-p53 is effective and safe treatments for advanced HCC.