Background E-selectin is an adhesion molecule expressed on activated endothelial cells. E-selectin plays an important role in the process of inflammation and is also involved in the mechanism of cancer metastasis regulating the adhesion of circulating cancer cells to the blood vessels. The aim of our study was to determine whether an association exists between its most common gene polymorphism, S128R, and gastric cancer (GC). Methods We performed a case-control study of 88 GC cases and 480 controls to analyze the association between E-selectin S128R gene polymorphism and GC susceptibility. The genotyping analysis was done by PCR-restriction fragment length polymorphism method. Results The E-selectin S128R C allele, CA and CC genotypes were over-represented among the GC cases. No statistically significant association was observed between E-selectin S128R polymorphisms and tumor characteristics. However, carrying the C allele was associated with poor survival. Conclusions The E-selectin S128R C allele may confer an increased susceptibility to gastric cancer development and correlate with a poor prognosis.