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Objective: To investigate the expression of cutaneous T cell lymphoma associated antigen 15 (CTAGE15) and its association with clinical prognosis of esophageal squamous cell carcinoma (ESCC) patients, as well as its effect on the proliferation, migration, and invasion abilities of ESCC cells. Methods: Kaplan-Meier analysis was used to analyze the effect of CTAGE15 on the prognosis of ESCC patients in public database. The mRNA expression levels of CTAGE15 in esophageal epithelial cells and ESCC cells were measured by qRT⁃PCR. Furthermore, the expression of CTAGE15 was detected in cancer and adjacent normal tissues from 120 ESCC patients with a complete follow⁃up information. COX proportional survival risk model was enrolled to analyze the survival risk factors of ESCC patients, and multivariate correlation analysis was used for the analysis of the association between CTAGE15 expression and the clinicopathology of ESCC patients. Kaplan⁃Meier analysis was employed to analyze the effect of CTAGE15 on the prognosis of ESCC patients. The knockdown of CTAGE15 in ESCC cells was achieved by using small interfering RNA (siRNA), and the changes in cell proliferation, migration, and invasion abilities of ESCC cells were assessed. Results: The public database showed that the CTAGE15 expression was significantly associated with overall survival (P < 0.05) and disease⁃specific survival (P < 0.05) in ESCC patients, and a higher GTAGE15 expression was correlated with a better survival. The qRT-PCR results revealed significantly high expression of CTAGE15 in ESCC tissues and cells, compared with normal esophageal epithelial tissues and cells. In addition, the expression of CTAGE15 was significantly associated with T stage and N stage of ESCC patients, and a higher GTAGE15 expression was associated with an earlier T stage and N stage. Knockdown of CTAGE15 enhanced the proliferation, migration, and invasion abilities of ESCC cells (P < 0.05). Conclusion: CTAGE15 expression is positively associated with the prognosis of ESCC patients, and it inhibits the proliferation, migration and invasion abilities of ESCC cells. [ABSTRACT FROM AUTHOR]