Abstract: OBJECTIVE To investigate the efficacy and safety of rituximab plus chemotherapy for the treatment of the diffuse large B-cell lymphoma combined with hepatitis B virus, so as to provide new ideas and programs for treatment of patients with diffuse large B-cell lymphoma combined with hepatitis B virus. METHODS A total of 72 cases of patients with diffuse large B-cell lymphoma combined with hepatitis B virus from Jan. 2010 to Feb. 2012 in our hospital were retrospectively analyzed. According to the treatment methods, 34 patients were selected as observation group using rituximab combined with chemotherapy, 38 patients were selected as control group treated with chemotherapy alone, and the results of the efficacy of two groups of patients, the degree of adverse symptoms and liver dysfunction, survival and HBV reactivation of the two groups were analyzed. RESULTS After treatment for follow-up comparison, 19 patients (55.88%) in observation group after CR were significantly better than 6 patients (15.79%) in control group (P<0.05). There was no significant difference between the two groups on related adverse symptoms. Comparison of liver and the extent of liver damage in observation group and control group, all patients in observation group were grade Ⅰ damage, and in control group, there were 1, 3, and 1 case of grade Ⅰ, Ⅱ, and III damage, respectively. By 3 years of follow-up records of 72 patients, it is found that 1, 2, 3-year deposit rates of observation group were significantly higher than those of control group (P<0.05). There was 1 case (2.94%) of patient with HBV reactivation in observation group, and no case in control group. CONCLUSION Rituximab combined with chemotherapy for diffuse large B-cell lymphoma combined with hepatitis B virus has a good effect, and its clinical application does not aggravate adverse symptoms in patients.