Abstract: Objective To investigate the relationship between single and double eyelids and esophageal cancer risk. Methods The prevalences of single and double eyelids and esophageal cancer, were recorded by questionnaires, interview (over 80% at home) in 2 262 case with esophageal squamous cell carcinoma and 3 459 controls and unconditional Logistic regression analysis was performed on clinicopathology. Results The prevalence of single and double eyelids in cases was higher than that in controls (P<0.001). Population with single eyelid had higher risk of esophageal cancer than those with double eyelids (OR=1.29,95%CI:1.15-1.44, P <0.001). Stratifi ed analysis by age, the subjects aged from 45 to 64 years with single eyelid had higher risk of esophageal cancer than those with double eyelids (OR:1.26-1.61,95%CI:1.08-2.02). Conclusion Single eyelid could be used as an indicator to indicate the high susceptibility of esophageal cancer and further provides clues to research links between dermatoglyph and molecular mechanism of esophageal cancer.