Perturbations in the apoptotic genes have been implicated in human malignancies. The purpose of the present study was to investigate the polymorphisms of -938C/A, Thr43Ala in anti-apoptotic B-cell lymphoma 2 gene (BCL2) and -248G/A in pro-apoptotic B-cell lymphoma 2-associated X protein gene (BAX) and to explore their role in influencing the susceptibility for development of esophageal cancer. A total of 205 esophageal cancer patients and 224 controls were enrolled in the present study. The genotype and allele distributions of -938C/A, ala43thr in BCL2 and -248G/A in BAX were analyzed in patients and controls, as well as the association of -938C/A genotype with clinical characteristics in patients. We found that homozygous -938A/A genotype of BCL2 gene was significantly associated with risk of developing esophageal cancer (χ2=9.269, P=0.002, OR=2.585, 95%CI = 1.380-4.842). Association with clinical characteristics showed that the patients with BCL2 -938A/A genotype were more likely to develop into poor differentiation compared with the AC and CC carriers (χ2=5.796, P=0.016, OR=4.039, 95%CI=1.200-13.596), and we found smokers were more present in the -938A/A genotype subgroup (χ2=5.095, P=0.024, OR=2.679, 95%CI=0.893-8.025). The present study revealed that the -938A/A genotype of BCL2 gene is associated with susceptibility of esophageal cancer. There appeared to be an impact of BCL2 -938A/A genotype on tumor differentiation and smoking. Further studies are needed in a larger population.