In the present study, we attempted to ascertain the methylation level and expression of PTPN22 in ESCC and the correlation between the PTPN22 methylation change and a series of clinicopathological parameters in a large sample of ESCC patients to elucidate the role of PTPN22 in the pathogenesis of ESCC and its potential role as a prognostic marker. Here, PTPN22 is linked to esophageal squamous cell carcinoma.