【Objective】To investigate the expression of eukaryotic translation initiation factor 5A2（EIF5A2）and its clinical significance in esophageal squamous cell carcinoma（ESCC）.【Methods】Immunohistochemistry was used to detect the expression of EIF5A2 protein in 135 cases of esophageal squamous cell carcinoma，and analyzed the correlation between the expression of EIF5A2 protein and clinicopathological parameters，and its prognosis value.【Results】Immunohistochemical analysis showed that 68 cases were overexpressed in 135 cases of ESCC. Pearson′s chi-square test indicated that the expression of EIF5A2 in ESCC was significantly correlated with T stage（P = 0.006），lymph node metastasis（P = 0.031）and clinic stage（P = 0.026）. The Cox proportional hazard model analysis showed that EIF5A2 was an independent prognostic risk factor for ESCC patients. Kaplan-Meier analysis showed that the median survival time of patients with the low expression was 72.5 months，which was significantly higher than that of patients with the high expression，the median survival time of it are 51.7 months（P < 0.05）.【Conclusion】The overexpression of EIF5A2 may contribute to the development and progression of ESCC and EIF5A2 could be a novel potential prognostic marker for ESCC.