BACKGROUND & AIMS: Adjuvant anti-viral therapy after curative therapy for HCC has been studied extensively but the true clinical benefit and the predictors of efficacy remain unclear. METHODS: MEDLINE, PubMed, and the Cochrane library were searched until December 2008, plus the meeting abstracts of the American Association for the Study of Liver Disease 2005- 2008. Randomized trials and cohort studies were included if the studies (1 ) enrolled HCC patients who had underlying chronic viral hepatitis B or C and had undergone curative surgery or ablation therapy; (2) consisted of one or more treatment arms with interferon- based therapy and a control arm of no anti-viral therapy; and (3) included recurrence-free survival of HCC as an endpoint. Meta-analysis and meta-regression were done according to the Cochrane guidelines. RESULTS: Thirteen studies (9 randomized trials and 4 cohort studies, totally 1180 patients) were eligible for meta -analysis. Surgery and ablation therapy were used in 9 and 8 studies, respectively. All studies used conventional interferon (natural or recombinant) as anti-viral therapy. Overall, interferon improved the 1- year, 2-year, and 3-year recurrence-free survival by 7.8% (95% CI 3.7-11.8 %), 35.4% (95% CI 30.7-40.0 %), and 14.0% (95% CI 8.6-19.4%), respectively (all p