Abstract: Objective To investigate the effect of CHOP chemotherapy regimen combined with rituximab on diffuse large B-cell lymphoma (DLBCL). Methods A total of 78 patients with DLBCL were divided into two groups according to the different treatment plan:observation group (n=41) and control group (n=37). The control group was given CHOP chemotherapy with cyclophosphamide 750 mg/m², intravenous drip, 1 times/day, d1; epirubicin 50 mg/m², intravenous drip, 1 times/day, d1; vincristine 1.4 mg/m², intravenous drip, 1 times/day, d1; dexamethasone 15 mg/m², intravenous drip, 1 times/day, d1-5, the observation group based on the control group combined with rituximab 375 mg/m², intravenous drip, 1 times/day, d0. When compared the clinical curative effect between the two groups, the level of inflammatory factors and adverse reaction conditions. Results The effective rate of TNF-α in the observation group(78.05%) was significantly higher than that in the control group(59.46%), P<0.05. After treatment, the level of TNF-α in the observation group was significantly higher than that in the control group (P<0.05), but the increase in the control group was not significant (P>0.05). The decrease in the observation group was significantly stronger than that in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion CHOP regimen combined with rituximab therapy can improve the clinical efficacy of DLBCL patients, the level of anti-inflammatory factor was increased and the expression of proinflammatory cytokines was decreased. The safety of anti-inflammatory factor was not significantly different from that of CHOP alone, worthy of clinical promotion.