To further evaluate the clinical influencing factors of rituximab in the treatment of diffuse large B cell lymphoma patients with hypergammaglobulinemia by studying the clinical efficacy of rituximab combined with chemotherapy in patients with hypergammaglobulinemia. 89 patients with diffuse large B cell lymphoma treated in our hospital from January 2011 to December 2020 were selected as subjects. After informed consent, the patients in the control group were divided into two groups: the control group was treated with conventional chemotherapy and the treatment group was treated with rituximab on the basis of conventional chemotherapy. Basic information such as age, sex, past medical history, clinical tumor stage and so on was collected. The venous blood was collected before and after treatment and the levels of hemoglobin, erythrocyte sedimentation rate, albumin, globulin, Lactate dehydrogenase and beta 2-microglobulin were measured by automatic biochemical analyzer and the levels of Immunoglobulin G, Immunoglobulin A and Immunoglobulin M were measured by immunoturbidimetry. Complete remission, partial response, stable disease and disease progression, were recorded and the total effective rate was calculated. There were 27 patients in the control group (14 males and 13 females, 9 patients with hyperimmunoglobulinemia), according to Ann Arbor staging, there were 1 case in stage I, 10 cases in stage II, 7 cases in stage III and 9 cases in stage IV. There were 62 patients in the treatment group, aged 56.3 +/- 14.2 y, including 25 males and 37 females, 18 patients with hyperimmunoglobulinemia and according to Ann Arbor staging, there were 7 patients in stage I, 16 patients in stage II, 10 patients in stage III and 29 patients in stage IV. There was no significant difference in age, sex, incidence of hyperimmunoglobulinemia, International prognostic index score, tumor stage and previous history between the two groups. There was no significant difference in the levels of hemoglobin, erythrocyte sedimentation rate, albumin, lactate dehydrogenase and beta 2-microglobulin between the control group and the treatment group before and after treatment. The erythrocyte sedimentation rate after treatment in the treatment group and the control group was lower than that before treatment and the difference was statistically significant (p<0.05). There was no significant difference in the levels of Immunoglobulin G, ImmunoglobulinA, ImmunoglobulinM and globulin between the control group and the treatment group before treatment, but after treatment, the level of globulin in the treatment group was significantly lower than that in the control group (p<0.05). After treatment with rituximab combined with chemotherapy, the levels of ImmunoglobulinG, ImmunoglobulinA, ImmunoglobulinM and globulin in the treatment group were significantly lower than those before treatment, while the levels of ImmunoglobulinG, ImmunoglobulinA and globulin in the control group were significantly lower than those before treatment, but there was no significant difference in the level of Immunoglobulin M before and after treatment. After rituximab combined with chemotherapy, the total effective rate of the treatment group was 82.3 %, which was much higher than that of the control group (55.6 %) and the difference was statistically significant (p<0.05). In the treatment group, the total effective rate of patients with hypergammaglobulinemia after rituximab combined chemotherapy was 85.4 %, which was much higher than that in the normal group (26. 8 %) and the difference was statistically significant (p<0.05). Rituximab combined with chemotherapy is effective in the treatment of diffuse large B-cell lymphoma with hypergammaglobulinemia. It can effectively reduce the level of immunoglobulin in vivo and provide reference for clinical treatment.