Esophageal cancer is a common cause of cancer-related deaths worldwide. Squamous cell carcinoma (SCC) is the major histological type of esophageal cancer in developing countries including China, and the prognosis is very poor. Many microRNAs are involved in several important biological and pathologic processes, and promote tumorigenesis. To better understand the prognostic and therapeutic roles of microRNAs in ESCC, we reviewed the diagnosis and prognosis associated oncogenic microRNAs (e.g. miR-21 and miR-17-92 cluster) and tumor suppressor microRNAs (e.g. miR-375, miR-133a and miR-133b), and diagnosis and prognosis associated oncogenic target genes (e.g. PDCD4 and CCND1) and tumor suppressor target genes (e.g. EZH2 and PDK1). We also summarized the prognostic microRNA and target gene pairs (e.g. miR-296 and CCND1, miR214 and EZH2). Taken together, our review highlights the opportunities and challenges for microRNAs in the molecular diagnosis and target therapy of ESCC.