This study was designed to investigate the association of the IL-8-251 T > A gene polymorphism with clinicopathological features and the prognostic role of the gene polymorphism in patients with gastric adenocarcinoma. The gene polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism method, followed by univariate and multivariate analyses to elicit its prognostic role. The frequency of IL-8-251 A/A, A/T and T/T genotypes were 11.0% (23/210), 43.8% (92/210) and 45.2% (95/210), respectively. The IL-8-251 gene polymorphism was closely correlated with depth of invasion (p = 0.007), grade of differentiation (p = 0.002) and TNM stage (p = 0.009). A/A genotype carriers showed more frequency of serosa involvement, low grade of differentiation and advanced stage of gastric carcinoma. IL-8-251 T > A gene polymorphism have no significant correlation with other clinicopathological features. The 5-year overall survival of IL-8-251 A/A genotype and T allele carriers were 30.8% and 59.2%, respectively. There is a significant discrepancy among the different genotype carriers. Multivariate analysis with the Cox regression model revealed that the IL-8-251 A/A genotype is an independent prognostic indicator (HR = 2.285, 95% Confidence Interval = 1.06-4.93, p = 0.035). We conclude that the IL-8-251 A/A genotype may indicate a poor prognosis for gastric adenocarcinoma patients.