Hepatitis B viral (HBV) reactivation in lymphoma patients undergoing chemotherapy is associated with significant morbidity and mortality. Increasingly, lamivudine is being used to prevent hepatitis B reactivation. To assess the effects of prophylactic lamivudine on reactivation and mortality following chemotherapy in lymphoma patients who are hepatitis B surface antigen (HBsAg)-positive, we searched Medline/PubMed, Ovid MEDLINE, EMBASE, Web of Knowledge and the Cochrane Library for studies through November 2013. Statistical analysis was performed using REVMAN. Fourteen studies consisting of 636 patients were included in the analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis due to HBV reactivation in patients with lamivudine prophylaxis was significantly lower than those with no prophylaxis. Risk ratios [RRs] were 0.25 (95% confidence intervals [CI] 0.13–0.51; P=0.0001), 0.40 (95% CI 0.26–0.63; P<0.0001), and 0.21 (95% CI 0.09–0.51; P=0.0005) respectively. In addition, patients given prophylactic lamivudine had significant reductions in overall mortality and mortality attributable to HBV reactivation compared with control group. Risk ratios [RRs] were 0.45 (95% CI 0.29–0.70; P=0.0004) and 0.41 (95% CI 0.20–0.84; P=0.01) respectively. Chemotherapy disruption was not significantly different between the two groups. Risk ratios [RRs] were 0.34 (95% CI 0.09–1.26; P=0.11). Prophylactic therapy with lamivudine for HBsAg-positive lymphoma patients who are undergoing chemotherapy may reduce the risk for HBV reactivation, hepatitis due to HBV reactivation, overall mortality and mortality attributable to HBV reactivation. Additionally, patients with preventive lamivudine had a trend towards the decreased incidence of chemotherapy disruption.