Abstract: Objective To investigate the clinical and prognostic significance of EphA2 expression in diffuse large B-cell lymphoma（DLBCL）.Methods The immunohistochemistry（EnVision method）was applied to detect the protein expression of EphA2 on tissue sections from 72 DLBCL and 10 normal lymph tissues. Then the relationships between EphA2 expression and clinicopathological variables including gender， age， stage， B symptoms， lactate dehydrogenase（LDH）， international prognostic index（IPI） and pathological type were analyzed. The DLBCL patients were followed up for medium progression-free survival（PFS）and overall survival（OS）. Multivariate analysis of these prognostic factors was then performed using the Cox proportional hazards. Results Positive expression rate of EphA2 was 58.3％（42／72）in DLBCL tissues， higher than 20.0％（2／10）of normal lymph tissues（P＜0.05）. EphA2 expression was related with staging and pathological type， but not with sex， age， B symptoms， LDH and IPI（P＞0.05）. The median PFS and OS of 72 DLBCL patients were 15.5 and 22.0 months. LDH was an independent prognostic factor for PFS and OS. IPI only was the independent prognostic factor for PFS， while staging and EphA2 protein expression were independent prognostic factors for OS（P＜0.05）. Conclusion There was a high expression rate of EphA2 protein in DLBCL， and its expression was related with staging and pathological type. The positive expression of EphA2 indicated a poor prognosis for DLBCL.