Abstract： Objective To investigate the expression and clinical significance of bcl-2 and NF-κB/ p65 in different subgroups of diffuse large B-cell lymphoma (DLBCL). Methods Immunohistochemical staining was used to detect the expressions of CD10, bcl-6, and MUM-1 in the DLBCL patients. According to immunohistochemical algorithm of Hans et al. DLBCL were subdivided into GCB and non-GCB/ABC subgroups and the expressions of bcl-2 and NF-κB/p65 were detected. The expressions of bcl-2 and NF-κB/ p65 in GCB DLBCL were compared with that in ABC DLBCL,and the correlation of bcl-2 and NF-κB/p65 expressions with survival in the two major subgroups of DLBCL were analyzed. Results The expression rates of bcl-2 and NF-κB/p65 proteins in DLBCL were 67.1% and 77.1%, and there was significant correlation between them. The expression rates of bcl-2 and NF-κB/p65 were 52.0 % and 56.0 % in GCB DLBCL, but were 75.6 % and 88.9 % in ABC DLBCL. The expression rates of two proteins were higher in ABC DLBCL than in GCB DLBCL. There was no significant correlation between bcl-2 and NF-κB/p65 protein expressions and overall survival within the GCB DLBCL subgroup, but bcl-2 and NF-κB/p65 expressions had a significant effect on overall survival within the ABC subgroup. Conclusion bcl-2 and NF-κB/p65 expressions are associated with poor survival in the ABC subgroup only. Hence, the significance of bcl-2 and NF-κB/p65 protein expressions should be assessed in the context of DLBCL subgroups in the future.