Our results demonstrated that the BCL-2 rs2279115 AA genotype was significantly associated with decreased ESCC risk compared with the CC genotype (OR = 0.72, 95% CI = 0.57–0.90, P = 0.005), especially in nonsmokers (OR = 0.42, 95% CI = 0.29–0.59, P = 0.001) or nondrinkers (OR = 0.44, 95% CI = 0.32–0.62, P = 0.002). The gene discussed is BCL2; the disease is esophageal squamous cell carcinoma.