The ataxia-telangiectasia group D complementing gene (ATDC) plays significant roles in various human cancers. However, the clinical significance of ATDC in esophageal squamous cell carcinoma (ESCC) has not been investigated. The ATDC messenger RNA level of 40 paired ESCC and nonneoplastic tissues were evaluated using quantitative real-time polymerase chain reaction, 10 pairs of which were also used for Western blot analysis. In addition, immunohistochemical staining was performed to detect the ATDC expression in 118 paraffin-embedded cancerous and matched nonneoplastic tissues, and the correlation of ATDC expression with the clinicopathological parameters and prognosis of the ESCC patients was analyzed. The quantitative real-time polymerase chain reaction, immunohistochemical staining, and Western blot results demonstrated that the expression level of ATDC was significantly higher in ESCC tissue than in matched noncancerous tissues. Both ATDC messenger RNA and protein expression in the ESCC tissue were significantly correlated with tumor differentiation, stage, and lymph node metastasis. However, there was no significant difference in ATDC expression based on patient age or gender. Moreover, the results of both univariate and multivariate analyses showed that increased ATDC expression was correlated with a shorter 5-year survival time for ESCC patients after surgery. We concluded that increased ATDC expression is associated with poor clinical outcomes and that this marker might be a useful indicator for prognosis and a promising target for therapy in ESCC patients.