Eukaryotic initiation factor 4A-II (eIF4A2) is an ATP-dependent RNA helicase involved in mRNA translation. Abnormal expression of eIF4A2 has been reported as a prognostic factor in different types of cancer. However, little is known regarding the function of eIF4A2 in esophageal squamous cell carcinoma (ESCC). In the present study, 253 samples were collected from patients diagnosed with ESCC, and the expression of eIF4A2 was detected by immunohistochemical staining. The clinicopathological and prognostic significance of eIF4A2 expression in ESCC were then statistically analyzed. The results demonstrated that eIF4A2 was specifically localized to the cytoplasm. Kaplan-Meier analysis also revealed that eIF4A2 expression was associated with the clinical prognosis of patients with ESCC. The median disease-free and overall survival times were 40 and 48 months for patients with low eIF4A2 expression, compared with 16 and 25 months in the high eIF4A2 expression group, respectively. In conclusion, high expression levels of eIF4A2 are associated with a poor prognosis and may be used as a potential prognostic indicator in patients with ESCC.