Compared with the BCL-2 rs2279115 CC genotype, a significantly decreased risk of ESCC was associated with AA genotypes only among males (OR = 0.70, 95% CI = 0.54–0.91, P = 0.008), but not among females (OR = 0.74, 95% CI = 0.42–1.32, P = 0.309). This evidence concerns the gene BCL2 and esophageal squamous cell carcinoma.