BACKGROUND. Hepatitis B virus (HBV) infection is a common disease in China. Severe hepatitis is a well recognized complication in HBV carriers with malignant disease who receive cytotoxic chemotherapy. The objective of the current study was to assess the value of antiviral lamivudine for reducing the incidence and severity of hepatitis in HBV carriers with lymphoma who receive chemotherapy. METHODS. Two groups were compared in this nonrandomized study. The prophylactic lamivudine group was comprised of 40 patients who received oral lamivudine at a dose of 100 mg daily before and until at least 8 weeks after they discontinued chemotherapy. The historic control group was comprised of 116 patients who received chemotherapy without lamivudine. The incidence and severity of hepatitis and other adverse clinical outcomes were compared between the two groups. Significant prognostic factors for the development of hepatitis were determined based on data derived from the control group. RESULTS. The two groups were comparable in most clinical baseline characteristics, including gender distribution, age, tumor types, primary treatment, hepatitis Be antigen status, and the use of anthracyclines or/and prednisone. In the prophylactic lamivudine group, there was significantly less incidence of hepatitis (17.5% vs. 51.7% in the control group; P 0.000); less severe hepatitis (according to World Health Organization [WHO] criteria) (10% with Grade 1, 5% with Grade 2, and 2.5% with Grade 3 hepatitis vs. 3.4% with Grade 1, 12.1% with Grade 2, 12.9% with Grade 3, and 23.3% with Grade 4 hepatitis in the control group; P = 0.000); and less disruption of chemotherapy (10.0% vs. 37.1% in the control group; P = 0.001). The overall mortality as a result of hepatitis in the prophylactic lamivudine group was lower compared with that in the control group, but the difference was not statistically significant (0.0% vs. 5.2%; P = 0.163). In the control group, the factor associated with a greater risk of developing hepatitis was the use of prednisone. In the prophylactic lamivudine group, I of 40 patients (2.5%) developed hepatitis that was attributable to HBV reactivation. Further examination demonstrated that this single patient had a variation of HBV with YMDD mutations after the use of lamivudine for 9.2 months. CONCLUSIONS. The results of the current study confirmed previous reports that lamivudine prophylaxis significantly reduced the incidence and severity of hepatitis in HBV carriers who were receiving chemotherapy for lymphoma. The chemotherapy disruption rate as a result of severe hepatitis also was decreased significantly.