The aim of this study was to compare the efficacy of rituximab plus CHOP regimen and CHOP regimen on newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL), and analyze their toxicities. A total of 69 patients were enrolled from July 2003 to Dec 2006. The patients were non-randomly were divided into 2 groups: 36 received CHOP alone (CHOP group) and 33 received rituximab plus CHOP (R-CHOP group). The complete response (CR) rates, overall survival (OS) and side events of the 2 groups were compared. The results showed that the CR rate in R-CHOP group was higher than that in CHOP group (69.7% vs 47.2%, p = 0.049); especially in patients of male, Ann Arbor III - IV and IPI 3 - 5 (p = 0.017, p = 0.005 and p = 0.000). The estimated mean OS in R-CHOP group was longer than that in CHOP group (45.7 months vs 35.2 months, p = 0.145), and also in the estimated mean progression free survival (PFS) (38.5 months vs. 24.6 months, p = 0.017). The major adverse events in combination group were infusion-related responses which could be well tolerated in patients, and hematological toxicities which were similar to those in CHOP group. In conclusions, Rituximab increases the therapeutic efficacy of CHOP regimen on newly diagnosed patients with DLBCL, without a clinically significant increase in toxicity.