To detect the role of GPER1 in different histological types of esophageal cancer, we examined the expression levels of GPER1 in esophageal cancer specimens by immunohistochemistry and followed these results by investigating the effect of GPER1 in esophageal cell lines in vitro via the treatment of specific agonist G1, antagonist G15, and knockdown of GPER1 expression by siRNA, thus providing a basis for analyzing the role of GPER1 in the sex bias and pathogenesis of esophageal malignancies. This evidence concerns the gene GPER1 and esophageal cancer.