BACKGROUND: Lymphoma combined with hepatitis B infection occupies a relatively higher incidence in China than that of in Europe and America. AIMS: To observe the efficacy and safety of rituximab in combination with chemotherapy in patients with B-cell non-Hodgkin's lymphoma (NHL) and hepatitis B virus (HBV) infection. METHODS: Ninety-two B-cell lymphoma patients with HBV infection in Sichuan Cancer Hospital from January 2009 to October 2015 were divided into two groups. Patients in Group A (n = 33) were treated with rituximab combined with chemotherapy, while Group B (n = 59) accepted chemotherapy alone. RESULTS: The effective rate (complete response + partial response) was 69.7% in Group A and 44.1% in Group B with significantly statistical difference (P = 0.018). Some of the patients got different grades of hepatic function damage during the period of chemotherapy, but there was no statistically significant difference between these two groups (P = 0.071). CONCLUSIONS: For CD20-positive NHL patients complicated with HBV infection, rituximab combined with chemotherapy modality is effective. The promise efficacy of this regimen could be achieved relying on controllable safety based on antiviral treatment.