MicroRNAs (miRNAs) are postulated to play important roles in oncogenesis. Recently, extracellular miRNAs were detected in plasma or serum of diseased subjects. However, the role of circulating miRNAs in plasma/serum remains to be elucidated. In this study, the relative expressions of miR-155, miR-183, and miR-20a in esophageal tissue were found to be significantly associated with increased risk for esophageal cancer. The relative expressions of circulating miR-155 and miR-183 were significantly reduced in cancer patients. Circulating miR-155 showed significantly higher risk for esophageal cancer when adjusted by smoking status and alcohol use. Circulating miR-155 was found to have significant diagnostic value for esophageal cancer as evidenced by a receiver operating characteristic curve area of 66%. However, Pearson analysis showed no statistical correlation in the relative miRNAs expression between plasma and esophageal tissues, which suggested different origins of circulating miRNAs distinct from tumor cell miRNAs. In conclusion, results suggest that circulating miR-155 in plasma may serve as a reliable, novel, noninvasive biomarker for early diagnosis and detection of esophageal cancer.