Background: Oesophageal carcinoma is one of the most frequently seen malignancies, and its incidence ranks third among men and fifth among women in China. Among all the histological categories, oesophageal squamous cell carcinoma (ESCC) accounted for the most of the cases. At present, there are few therapeutic methods applied in clinical practice for ESCC due to the limited evidence with respect to the underlying signaling pathways and the miRNAs related to the ESCC. Methods: To identify the differentially-expressed miRNAs (DE-miRNAs) in different stages of ESCC, we performed a microarray on 92 ESCC and 3 normal tissues. At the mean time, the potentially targeted genes as well as the highly-enriched signaling pathways and the relevant protein–protein interaction (PPI) network were analyzed and constructed by using a series of bioinformatic methods. Moreover, the identified DE-miRNAs in different stages of the ESCC were verified by using the TCGA dataset. Results: According to our analysis, overall 37 DE-miRNAs were identified, including 6 up-regulated miRNAs and 31 down-regulated miRNAs. 1884 genes were selected as the potentially targeted genes for the above miRNAs, most of which were found to be enriched in the PI3K-Akt signaling pathway and the Hippo signaling pathway. Based on the PPI network we constructed, PIK3R1 and NOTCH1 were considered as the potential hub genes. Conclusion: Our study provided additional explanations regarding the molecular mechanisms and prognosis of ESCC through the identification of a number of potential targeted genes of the DE-miRNAs in different stages of ESCC as well as the mostly enriched signaling pathways of the above genes, which could promote the development of the targeted treatment and improve the prognosis evaluation of ESCC.