Aliment Pharmacol Ther 2011; 33: 1104–1112 Summary Background  The role of anti‐viral therapy in prevention of hepatocellular carcinoma (HCC) recurrence is to be defined. Aim  To investigate the role of anti‐viral therapy in prevention of tumour recurrence after curative treatment of hepatitis B virus (HBV)‐related HCC. Methods  A systematic electronic search on keywords including HCC and different anti‐viral therapies was performed through eight electronic databases, including Medline, EMBASE and Cochrane Databases. The primary outcome was HCC recurrence after curative treatment of HBV‐related HCC. The secondary outcomes were mortality related to HCC, mortality related to liver failure and the overall mortality. Results  Nine cohort studies were included with a total number of 551 patients: 204 patients with anti‐viral treatment group and 347 patients without anti‐viral treatment (control group). There was significant difference in the incidence of HCC recurrence in favour of the anti‐viral treatment group (55% vs. 58%; odds risk (OR) = 0.59, 95% CI 0.35–0.97, P = 0.04). The risk of HCC was reduced by 41% in the anti‐viral treatment group. There were also significant differences in favour of anti‐viral treatment group in terms of liver‐related mortality (0% vs. 8%; OR = 0.13, 95% CI 0.02–0.69, P = 0.02) and overall mortality (38% vs. 42%; OR = 0.27, 95% CI 0.14–0.50, P < 0.001). Conclusions  Anti‐viral therapy has potential beneficial effects after the curative treatment of HBV‐related hepatocellular carcinoma in terms of tumour recurrence, liver‐related mortality and overall survival. Anti‐viral therapy should be considered after curative treatment of hepatocellular carcinoma.