Objective To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with sorafenib in treatment of patients with non-resected middle stage hepatocellular carcinoma (HCC). Methods From July 2009 to July 2011, 38 middle stage HCC patients treated with TACE plus sorafenib were included in the TACE+sorafenib group and the other 38 patients with similar baseline characteristics receiving TACE alone were selected in the TACE group. All the patients belonged to the Barcelona Clinic Liver Cancer (BCLC) stage B. The adverse events of the TACE+sorafenib group and the overall survival of the two groups were analyzed. Results All the patients treated with sorafenib experienced at least one drug-related adverse event during the study, including 7 (18.4%) experienced drug-related grade 3 adverse events, with no grade 4 or higher adverse events occurred. The median overall survival time was 11 months (95% CI: 7.4-14.6 months) for the TACE group and 15 months (95% CI: 8.4-21.6 months) for the TACE+sorafenib group, showing significant difference between the two groups (P=0.019). Conclusion The combination of sorafenib with TACE is well tolerated in non-resected middle stage HCC patients, with no severe adverse events and can effectively improve the overall survival time of patients.