〔Abstract〕 Objective To investigate the risk factors associated with the presence of multiple Lugol-voiding lesions(LVLs) in patients with early esophageal cancer and the correlation with alcohol dehy-drogenase 1B(ADH1B) and aldehyde dehydrogenase 2(ALDH2) polymorphisms. Methods Patients who underwent endoscopic submucosal dissection due to early esophageal cancer were divided into group with multiple LVLs and group without multiple LVLs based on their endoscopic features. Their clinical data and the genotype of ADH1B and ALDH2 were collected and SPSS 27.0 was used to statistically analyze the above data. Results A total of 83 subjects were included in the study, 23 had multiple LVLs, most of them were seen in males, alcohol drinkers, and smokers with smoking index≥1 000, and multivariate analysis showed that alcohol consumption was an independent risk factor for it(OR=6.215,P=0.008). The gene polymorphism of ADH1B and ALDH2 and their interactions did not have any significant correlation with multiple LVLs. However, among alcohol drinkers, there was a 12-fold increased risk of multiple LVLs in patients carrying the ALDH2 A allele and drinking ≥50 g per day compared to those carrying the ALDH2 GG genotype and drinking<50 g per day(P=0.045). Conclusion Alcohol consumption is an independent risk factor of multiple LVLs of the esophageal mucosa in patients with early esophageal cancer, and heavy alcohol consumption in carriers of the ALDH2 A allele will significantly increase the risk of multiple LVLs, and such patients should be closely followed up with endoscopy.