Objective To investigate the expression of miR-125a-5p in diffuse large B-cell lymphoma and the relationship among the levels of NF-κB/p65,Bcl2,Caspase3 and Ki-67 protein in clinicopathological features, and the potential prognostic value. Methods A total of 84 cases of DLBCL were enrolled in this study. At the same time,10 cases of reactive hyperplasia tissues were used as the control group. The expression of miR-125a-5p was examined by SYBR Green real-time reverse transcriptase polymerase chain reaction(real-time RT-PCR). The expression of NF-κB/p65,Bcl2,Caspase3,Ki-67 was detected by the immunohistochemical staining assay. The clinical pathological data was collected and some patients were followed up. The clinical data was used for analysis of the prognosis of patients. Results MiR-125a-5p was shown up-regulated in the DLBCL samples ,which was (4.99 ± 8.22)times of that in the reactive hyperplasia samples(P=0.002). The up-regulation of miR-125a-5p in DLBCL was correlated with non-GCB subtype(P=0.027). The up-regulation of miR-125a-5p in DLBCL was sig-nificantly correlated with the expression of NF-κB/p65,Bcl2 and Caspase3(P=0.031,0.030,0.022). There was a significant correlation between non-GCB subtype and NF-κB/p65 level in DLBCL(P=0.002). Kaplan-Mei-er survival analysis showed that the high expression of miR-125a-5p was associated with the prognosis of DLBCL pa-tients(P=0.038). Multivariate Cox regression analysis showed that the high expression of miR-125a-5p may be an independent risk factor for the prognosis of DLBCL(P=0.013). Conclusions MiR-125a-5p may play an im-portant role in the diagnosis of DLBCL. The up-regulation of miR-125a-5p in DLBCL may affect the activation of NFκB/p65,especially in the non-GCB subtype. The up-regulation of miR-125a-5p in DLBCL may influence the de-velopment of tumor via apoptosis pathway. The expression of miR-125a-5p is associated with the poor prognosis of patients,which can be regarded as an independent risk factor for the prognosis of DLBCL.