RASSF1A promoter hypermethylation could significantly increase 6-fold and 8-fold higher risk to ESCC and GCA development, respectively, and induce the inactivation of RASSF1A protein expression both in ESCC and GCA, which indicate that RASSF1A promoter hypermethylation may play an important role both in esophageal and gastric cardia carcinogenesis. This evidence concerns the gene RASSF1 and esophageal squamous cell carcinoma.