Although CRNN has been reported to be downregulated in esophageal adenocarcinoma (EAC) or ESCC [6–9], and genetic variants of CRNN appeared to interacte with tobacco smoking that contributes to the risk for ESCC [10], the precise mechanism underlying the involvement of CRNN in ESCC remains to be elucidated. This evidence concerns the gene CRNN and esophageal squamous cell carcinoma.