Taken together, we postulated that the genetic mutation occurred in the exon 5 of BTLA gene might influence the function of BTLA‐HVEM pathway, where this signaling pathway has been proven to decrease local immune response in the tumor tissue of ESCC.33 In the future, more replicated studies about this SNP are required to confirm our hypothesis in esophageal carcinogenesis. Here, BTLA is linked to esophageal squamous cell carcinoma.