To investigate the clinical features and prognostic factors of patients with primary extranodal diffuse large B-cell lymphoma (DLBCL) in the rituximab era. The continuous data of newly diagnosed DLBCL patients with complete case data and first-line treated with rituximab, cyclophosphamide, epirubicin, vincristine, prednisone (R-CHOP) or R-CHOP treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to November 2023 were retrospectively analyzed. The clinical and molecular immunological features and prognosis of extranodal DLBCL were analyzed, Logistics regression model was used to analyzed the influencing factors of patients prognosis. A total of 237 patients were enrolled, of which 54.4% (129 cases) were primary extranodal sources of DLBCL, and the most common extranodal sites were as follows: stomach (19.4%), colon (14.7%), tonsils (12.4%), skin/muscle (9.3%), central (7.7%), nasal/nasopharynx (6.2%), bone marrow (5.4%), testes (4.7%). The 3-year PFS and OS of DLBCL patients with extranodal involvement of bone marrow, central, liver, gastrointestinal or pulmonary origin were significantly lower than those of other patients with extranodal DLBCL of non-special site origin, and the difference was statistically significant (PFS: 65.2% vs 76.7%, P =0.008; OS: 82.6% vs 88.3%, P =0.04). Multivariate analysis showed that the prognostic factors affecting OS included NCCN-IPI score >3 (OR : 0.142, 95%CI : 0.041-0.495, P =0.002), non-germinal center source (OR : 2.675,95%CI :1.069-6.694,P =0.036), and DEL patients (OR : 0.327, 95%CI : 0.129-0.830, P =0.019). An NCCN-IPI score >3 was the only independent adverse prognostic factor for PFS (OR : 0.235, 95%CI : 0.116-0.474, P < 0.001). Patients with primary extranodal source DLBCL are more common in gastrointestinal involvement, and the overall prognosis is worse than that of patients with lymph node origin. NCCN-IPI score is an important independent adverse prognostic factor for predicting overall survival and progression-free survival in patients with primary extranodal diffuse large B-cell lymphoma.