OBJECTIVE To investigate the safety and effectiveness of combined (131)I-metuximab and transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS One hundred and eighty-five patients (159 men and 26 women) with advanced HCC were enrolled in this study from February 2009 to July 2011. There were 95 patients in the combined metuximab and TACE group, and 90 patients in the TACE only group. The patients were followed for 12 mo. Clinical symptoms, blood cell counts, Karnofsky Performance Score (KPS) evaluation and therapeutic effects according to the Response Evaluation Criteria in Solid Tumors were recorded and evaluated. RESULTS The 1-mo effective rates (complete response + partial response + stable disease) of the test group and control group were 71.23% and 38.89%, respectively (P < 0.001). The 6-, 9- and 12-mo survival rates were 86.42%, 74.07% and 60.49% for the test group and 60.0%, 42.22% and 34.44% for the control group (P < 0.001). The incidence of adverse events (gastrointestinal symptoms, fever and pain) and blood cell toxicity were significantly higher for the test group than for the control group (P < 0.001). No severe (131)I-metuximab-related complications were identified. With respect to efficacy, patients in the test group had greater improvement in tumor-related pain (P = 0.014) and increase in KPS (P < 0.001) than those in the control group. CONCLUSIONS Combination of (131)I-metuximab and TACE prolonged the survival time in patients with HCC compared with TACE alone. The combination treatment was safe and effective.