In this study, we have found that PRSS8 promoter was hypermethylated in esophageal squamous cell carcinoma tissues and cancer cell lines, resulting in downregulation of PRSS8 at mRNA and protein levels, which was supported by the GEO Profiles (http://www.ncbi.nlm.nih.gov/geoprofiles/) and Oncomine (http://www.oncomine.com) online data (Supplemental Figure 1) showing that PRSS8 was significantly reduced in esophageal squamous cell carcinoma and adenocarcinoma in comparison with the adjacent non-tumor esophagus. Here, PRSS8 is linked to adenocarcinoma.