Objective:To investigate clinical curative effect of trans-arterial chemo-embolization (TACE) in combination with radio-frequency ablation (RFA) for the treatment of massive primary hepatocellular carcinoma so as to provide theoretical basis for clinical practice.Methods: 60 patients with massive primary hepatocellular carcinoma were divided into control group (30 cases) and observation group (30 cases) according to the different treatment methods. The patients of control group received the treatment of TACE while the patients of observation group received the combined treatment of TACE and RFA, at the same time, all of the patients of two groups received the supportive treatment for protecting liver. After the operation, the necrosis situations of patients in the two groups were evaluated by using enhanced CT, and their complication and survival time were recorded. Besides, the changes of series of indexes including blood routine, hepatic and renal function and immunologic function were monitored. Based above data, the curative effect and safety of the two therapeutic methods were compared and analyzed. Results: After treatment, the 6 months, 1 year, 2 years, 3 years survival rate of observation group were significantly higher than that of control group (x2=5.787,x2=6.814,x2=4.802,x2=4.622,P<0.05). And the TBIL, ALT and AFP of observation group were significantly lower than that of control group (t=5.775,t=3.332,t=10.231,P<0.05). Besides, the CD3+, CD4+/CD8+, NK cells and TNF-α of observation group were significantly higher than that of control group (t=6.434,t=5.125,t=6.017,t=4.669,P<0.05).Conclusion: The curative effect of TACE combined with RFA is significantly better than that of single TACE, and it is worthy in clinical popularization and application.