Abstract: Objective :To detect aberrant CpG island methylation of promoter of the p16 and FHIT gene in tissues of esophageal precancerous lesions. Methods :Specific methylation-specific PCR (MSP) was used to detect CpG island methylation status of the p16 and FHIT gene in esophageal precancerous lesions, carcinoma in situ (CIS) and infiltrated carcinoma of esophageal squamous cell, and comparison analysis was performed in their corresponding nonmalignant tissues adjacent to the lesions and chronic esophagitis. Results :In total 95 esophageal lesions, the frequency of the p16 methylaion in mild, moderate and severe atypical hyperplasia, CIS and infiltrated carcinoma of esophageal squamous cell was 22.73%, 59.09V, 78.57% and 64.86%, and the frequency of the FHIT methylaion was 22.73%, 45.45V, 64.29V and 67.57%, respectively. Whereas in the 95 cases with corresponding noncancerous tissues of the esophageal lesions, 16 were not detected successfully, and in the other 79 cases, five of the 79 cases (6.33%) in p16 and three (3.80%) in FHIT were found to be methylated. The significant difference in methylation of both genes between the various stages of lesions and the corresponding nonmalignant tissues was observed (B=0.000). In 10 chronic esophagitis, 1 (10%) was found p16 methylaion and none FHIT methylation was found. Conclusions :P16 and FHIT methylaion exist in the esophageal precancerous lesions, and it might be one of the early events in the occurrence of esophageal carcinoma.