BACKGROUND AND AIM: Reactivation of hepatitis B virus (HBV) replication happens in patients who receive transarterial chemoembolization or systemic chemotherapy for hepatocellular carcinoma (HCC). The incidence and risk factors of HBV reactivation during the perioperative period in HCC patients receiving hepatic resection is unknown. METHODS: Between May 2009 and November 2010, 164 consecutive patients with HBV-related HCC who underwent hepatic resection were prospectively enrolled in the study. Among these, 126 patients received antiviral treatment before the operation (the antiviral group) and 38 patients did not receive any antiviral treatment (the non-antiviral group). RESULTS: Ten patients (6.1%) developed HBV reactivation perioperatively (within 1 month after hepatectomy). The incidence of HBV reactivation in the antiviral group and non-antiviral group were 1.6% (2/126) and 21.1% (8/38), respectively (P < 0.001). On univariate analysis, preoperative HBV DNA < 1.0 × 10(3) copies/mL and non-antiviral therapy were significantly correlated with the occurrence of HBV reactivation (P = 0.044 and P < 0.001, respectively). Only non-antiviral therapy remained as a predictive factor on multivariate analysis (odds ratio, 15.46; 95% confidence interval, 2.80-85.46, P = 0.002). The recovery of liver function (defined as a decrease of alanine aminotransferase back to normal) was achieved in 86.8% (132/152) patients without HBV reactivation and in 37.5% (3/8) patients with HBV reactivation when evaluated on day 30 after hepatectomy (P < 0.001). CONCLUSION: Hepatectomy could reactivate HBV replication during the perioperative period, especially in patients who did not receive any antiviral therapy. A close monitoring of HBV DNA during the perioperative period was necessary irrespective of the preoperative HBV DNA level. Once HBV was reactivated, antiviral therapy should be given.