Abnormally expressed microRNAs (miRNAs) and genes have been found to play key roles in esophagealsquamous cell carcinoma (ESCC), but little is known about the underlying mechanisms. The aim of this paperwas to assess inter-relationships and the regulatory mechanisms of ESCC through a network-based approach.We built three regulatory networks: an abnormally expressed network, a related network and a global network.Unlike previous examples, containing information only on genes or miRNAs, the prime focus was on relationships.It is worth noting that abnormally expressed network emerged as a fault map of ESCC. Theoretically, ESCCmight be treated and prevented by correcting the included errors. In addition, the predicted transcription factors(TFs) obtained by the P-match method also warrant further study. Our results may further guide gene therapyresearchers in the study of ESCC.