Liver resection may be beneficial in intermediate-stage hepatocellular carcinoma (HCC), though the benefit of postoperative anti-hepatitis B virus (HBV) therapy in these patients remains unclear. In this study, we sought to evaluate the efficacy of postoperative anti-HBV for intermediate-stage HCC patients who underwent radical liver resection.According to inclusion and exclusion criteria, this study enrolled 202 HCC patients who underwent liver resection and had a high HBV-DNA load. The patients were divided into 2 groups on the basis of postoperative anti-HBV therapy: group A included patients undergoing postoperative anti-HBV therapy, whereas group B patients did not receive any postoperative anti-HBV therapy. Factors including baseline demographics, tumor characteristics, overall long-term survival, tumor-free survival, and tumor recurrence rate were compared between the 2 groups. Moreover, univariate and multivariate analyses were used to identify risk factors of HCC recurrence.Baseline demographics and tumor characteristics were comparable between the groups. The 1-, 3-, and 5-year overall survival rates in group A were 91.3%, 80.9%, and 66.1%, respectively, values that were significantly increased compared with group B (91.7%, 60.7%, and 52.4%, respectively, P = .019). Group A patients also exhibited enhanced 1-, 3-, and 5-year tumor-free survival compared with group B patients (87.0%, 67.0%, and 62.6%, respectively, in group A; 82.1%, 50.0%, and 42.9% in group B, P = .002). In addition, the tumor recurrence rate in group B was significantly increased compared with group A (P < .01). Univariate and multivariate analyses indicated lack of postoperative anti-HBV therapy [hazard ratio (HR) = 0.882; 95% confidence interval (CI), 0.712-0.938; P = .042] to be a predictor of tumor recurrence.For intermediate-stage [Barcelona Clinic Liver Cancer (BCLC) stage B] HCC with a high HBV-DNA load, postoperative anti-HBV therapy after curative resection should be routine adjuvant therapy.