Abstract: Objective To investigate the clinical effect of surgical operation combined with gene therapy in preventing postoperative recurrence of hepatocellular carcinoma ( HCC) . Methods A total of 102 patients with single HCC ( TNM stage 1-2, tumor diameter < 10 cm) who were admitted to Beijing You An Hospital, Capital Medical University, from July 2006 to February 2013 were enrolled, and among these patients, 60 underwent the gene therapy with recombinant adenovirus containing thymidine kinase suicide gene ( ADV-TK) before and after surgery ( gene group) and 42 underwent surgical resection alone ( surgery group) . The patients were followed up regularly after surgery to observe postoperative recurrence. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The log-rank test was used for the analysis of cumulative recurrence rate, and univariate and multivariate Cox regression analyses were used to identify influencing factors for recurrence rate. Results The 1-, 3-, and 5-year recurrence rates of tumor were 13. 8%, 33. 7%, and 47. 7% in the gene group and 18. 5%, 53. 2%, and 69. 2% in the surgery group, and there was a significant difference between the two groups ( χ2= 2. 643, P = 0. 041) . The gene group had a significantly higher proportion of patients with pyrexia after surgery than the surgery group, and there were no significant differences in the incidence rates of other complications and length of hospital stay between the two groups. The multivariate analysis showed that gene therapy was an independent influencing factor for cumulative rumulative recurrence rate ( odds ratio = 2. 752, 95 confidence interval: 1. 164-4. 251, P = 0. 038) . Conclusion Gene therapy combined with surgical resection can effectively reduce postoperative recurrence of tumor, and therefore, it holds promise for clinical application.