Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1 beta and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1 beta (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1 beta -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11-0.62; p = 0.002; OR = 0.462; 95% CI = 0.253-0.845, p = 0.01). In conclusion, subjects with IL-1 beta -511TT genotype or IL-1 beta*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population.