Expression of Eag1 was detected in resected esophageal squamous cell carcinomas tissues and matched tissues by immunohistochemistry and RT-PCR. Positive expression of Eag1 protein was 75% (51/68), and mRNA was 73% (8/11) in primary cancer tissues. Eag1 protein positively stained in all 10 metastatic lymph nodes. Eag1 protein and mRNA were negatively expressed in all non-cancerous matched tissues. Eag1 protein was associated with depth of penetration (P = 0.023), but not associated with other clinicopathological factors. Eag1 protein positive group had a significantly shorter survival time than the negative group (P = 0.005). Survival rates at each time-point for the positive group were lower than that for the negative group (P = 0.006), and Eag1 was identified as an independent prognostic factor of long-term survival (P = 0.016). In conclusion, Eag1 was aberrantly expressed in ESCC and correlated with poor prognosis after surgery.