Objective To study the expression of ubiquitin-activating enzyme E1 (UBE1) and Bcl-2 in diffuse large B cell lymphoma (DLBCL) and its clinicopathological relevance. Methods Tumor tissues were collected from 80 DLBCL patients, and tissues from 30 patients with reactive lymphoid hyperplasia (RH) were taken as controls. Immunohistochemistry detection (EnVision method) was used to detect the expressions of CD10, Bcl-6 and MUM1 in DLBCL tissues for immunology typing of GCB or ABC. The expression of UBE1 and Bcl-2 proteins in DLBCL tissues and RH tissues was assayed by immunohistochemical staining, and its correlation with patients’ clinical pathological indices were analyzed. We also analyzed the correlation of UBE1 expression with Bcl-2 expression in DLBCL tissues. Results The positive rates of UBE1 were 65.0% (52/80) in DLBCL tissues and 13.3%(4/30) in RH tissues (P<0.05). The positive rates of UBE1 were 53.3% (16/30) for GCB type DLBCL and 72.0%(36/50) for ABC type (P<0.05). The positive rates of Bcl-2 were 51.3% (41/80) in DLBCL tissues and 10.0% (3/30) in RH tissues (P<0.05). The positive rates of Bcl-2 were 36.7%(11/30) for GCB type DLBCL and 60.0% (30/50) for ABC type (P<0.05). The positive rate of UBE1 was correlated with age and the extranodal involvement site (P<0.05). The positive rate of Bcl-2 was correlated with age, Ann Arbor stage, extranodal involvement site and international prognostic index (P<0.05). UBE1 expression was positively correlated with Bcl-2 in ABC type DLBCL (r=0.582, P=0.001). Conclusion UBE1 and Bcl-2 proteins are highly expressed in ABC type DLBCL tissues, which probably plays a role in the development and progression of DLBCL. High expression of UBE1 and Bcl-2 may indicate poor prognosis of DLBCL patients.