In present study, we found that ZNF282 was frequently overexpressed in ESCC compared with normal esophageal epithelium (47.2% vs 5.7%, p<0.001) and its overexpression was an unfavorable prognostic indicator in ESCC in both univariate and multivariate survival analysis (both p<0.001). This evidence concerns the gene ZNF282 and esophageal squamous cell carcinoma.