Objectives: Major adjuvant therapies (ATs) for resected hepatocellular carcinoma (HCC) include chemotherapy, internal radiation therapy (IRT), interferon therapy (IFNT) and immunotherapy but the optimum regimen remains inconclusive. We aim to compare these therapies in terms of patient survival and recurrence rates.

Methods: We searched PubMed, EMBASE and Cochrane library databases for randomized trials comparing the above four therapies until 31 March 2014. We estimated the HRs for survival and ORs for overall recurrence among different therapies. Toxic effects were also evaluated.

Results: Fourteen eligible articles were included. IFNT improved 5-year survival greatly (HR 1.81, 95% CI 1.01–3.81, P = 0.034), whereas chemotherapy (HR 0.33, 95% CI 0.03–2.02), IRT (HR 0.31, 95% CI 0.02–3.33) and immunotherapy (HR 0.73, 95% CI 0.05–9.12) all provided a poorer survival outcome after 1-year. Similarly, for 5-year survival rates, although differing, IRT did not provide a significant improvement in survival (HR 1.38, 95% CI 0.34–5.19) compared with IFNT. Chemotherapy (HR 0.49, 95% CI 0.18–1.14) and immunotherapy (HR 0.56, 95% CI 0.17–1.59) did not appear to provide benefit over IFNT. Chemotherapy was ranked the worst in overall recurrence (OR 0.99, 95% CI 0.18–5.38) and most likely to cause toxic effects.

Conclusions: IFNT was the most efficacious AT regimen both for short and long term survivals. Immunotherapy and IFNT were the most two effective in preventing overall relapse for resected HCC.