Compared with the previous studies, our analysis, investigating the molecular effects of the HULC polymorphism in both the histopathological and laboratory prognostic markers of interest in terms of EAC/ESCC subtypes, PNI, LVI, PVI, G Status, SRC, and Intestinal versus Diffuse subtypes, as well as CEA and Ca19.9, revealed no association in any of the genetic models AC/AA, CC/AA, and C/A alleles. Here, HULC is linked to esophageal squamous cell carcinoma.