Abstract: Objective: Interleukin-8 (IL-8), a member of the CXC chemokine family, is an important activator and chemoattractant for neutrophils.It is implicated in a variety of inflammatory diseases, and is also found as a potent angiogenic factor in-volved in tumor invasion and metastasis.The aim of this study is to investigate whether the-251A/T polymorphism of the IL-8 promoter is associated with susceptibility to esophageal squamous cell carcinoma in the region south to Taihang mountain, a high incidence region in China. Methods: We conducted a population-based case control study in 320 pa-tients with esophageal squamous cell carcinoma and 404 healthy controls.IL-8 genotypes were determined by PCR with restriction fragment length polymorphism (PCR-RFLP). Results: The overall distribution of IL-8-251 genotype and al-lelotype in the esophageal squamous cell carcinoma patients and controls were not significantly different (P>0.05).A fami-ly history of upper gastrointestinal cancer and smoking significantly enhanced the risk of developing esophageal squamous cell carcinoma (adjusted OR=1.721 and 1.684, 95%CI=1.251-2.367 and 1.215-2.336).Stratification analysis by smoking status and family history of upper gastrointestinal cancer found that, compared with the T/T genotype, the A/A genotype significantly increased the risk of developing esophageal squamous cell carcinoma among the individuals with a family his-tory of upper gastrointestinal cancer (adjusted OR=2.378, 95%CI=1.075-5.258), while IL-8-251A/T polymorphisms did not increase the risk of developing esophageal squamous cell carcinoma in other subgroups. Conclusion: The IL-8-251A/T polymorphism is not associated with the incidence of esophageal squamous cell carcinoma in the Taihang moun-tain area, but the-251A/A genotype increases the risk of developing esophageal squamous cell carcinoma among the in-dividuals with a family history of upper gastrointestinal cancer.