Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in China.To reduce the high morbidity and mortality of the disease, sensitive and specific biomarkers for early detection are urgently needed.The tumor-specific microRNAs seem to be potential biomarkers for early diagnosis and treatment of cancers.In this study,differentially expressed microRNAs in tumor tissues and adjacent non-tumor tissues were detected by microRNA microarray.Stem-loop real-time reverse transcription PCR was conducted to verify the candidate microRNAs discovered by microarray.The result showed that hsa-miR-338-3p, hsa-miR-218 and hsa-miR-139-5p were down-regulated in tumor tissues compared with adjacent non-tumor tissues, while hsa-miR-183, hsa-miR-574-5p,hsa-miR-21* and hsa-miR-601 were up-regulated in tumor tissues.Multiple regression analysis revealed the aberrant expression of hsa-miR-338-3p, hsa-miR-139-5p, hsa-miR-574-5p and hsa-miR-601 increased the risk of esophageal cancer.Furthermore, we found hsa-miR-21* was significantly increased in heavy drinking patients.It is concluded that there is a set of differentially expressed miRNAs in esophageal cancer, which may be associated with the incidence and development of esophageal squamous cell carcinoma.It holds promise that differential expression profile of microRNAs in esophageal squamous cell carcinoma may be promising biomarkers for the early screening of high risk population and early detection.