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We performed this study to reassess the prognostic factors of diffuse large B-cell lymphoma (DLBCL) in the era of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Chinese population. One hundred and twenty-five consecutive patients with DLBCL were enrolled in this study from February 2000 to September 2006. They had received six courses of R-CHOP regimen consisting of rituximab 375 mg/m(2), intravenously, D1; cyclophosphamide 750 mg/m(2), bolus infusion, D2; doxorubicin 50 mg/m(2), bolus infusion, D2; vincristine 1.4 mg/m(2), bolus infusion, D2; and prednisone 60 mg, orally, D2-6. All the patients were evaluated and followed-up after the treatment. Eighty-six out of 125 enrolled patients (68.8%) achieved complete response (CR), 16 patients (12.8%) achieved partial response (PR), 11 patients (12.8%) achieved stable disease, and 12 patients (9.6%) experienced progressive disease (PD). In univariate analysis, IPI factors, except for age, was correlated with the treatment outcome of complete remission; however, only early clinical stages and absence of bulky disease was statistically significantly associated with the better CR rate. Lactate dehydrogenase (LDH), extranodal diseases, bulky disease, and obtaining CR after completion of four courses of treatment was correlated with TTF (P = 0.038, 0.044, 0.034, and 0.000, respectively); performance status, LDH level, number of extranodal diseases, and obtaining CR after completion four courses of treatment significantly influenced OS (P = 0.027, 0.000, 0.019, and 0.000, respectively); and presence of bulky disease and obtaining CR at the end of fourth cycle of treatment were significantly correlated with DFS in multivariate analysis (P = 0.006 and 0.001, respectively) in Cox regression. IPI is still important in predicting the prognosis in the R-CHOP era in DLBCL; however, obtaining CR after four cycles of R-CHOP and presence of bulky disease should be considered together.