Integrative central axis of lncRNA-miRNA-mRNA plays pivotal roles in tumor development and progression. However, the regulatory role of lncRNA-miRNA-mRNA in esophageal cancer remains elusive. TCGA database was utilized to investigate the differential expression of lncRNA, miRNA and mRNA in esophageal cancer (ESCA) and normal esophageal tissues, and GEO database was used to further validate the expression profile of key genes. Differential lncRNAs in TCGA database were submitted to Starbase, and lncRNAs related to overall survival were analyzed using Kaplan-Meier and log-rank test. We found 145 lncRNAs, 112 miRNAs and 2000 protein coding mRNAs were differentially expressed in ESCA samples, which were tightly involved in chromosome segregation, extracellular matrix assembly by GO assay, and KEGG assay revealed the correlation of differentially expressed genes with cell cycle, apoptosis and cGMP-PKG signaling pathway. Furthermore, there were 291 nodes in ceRNA network, which consisted of 40 lncRNAs, 28 miRNAs and 233 mRNAs, and formed 677 relations. Furthermore, 6 of 10 lncRNAs in TCGA database were consistent with GEO database, and expressions of 10 mRNAs in TCGA database all exhibited the same tendency with GEO database. Notably, we found 8 lncRNAs (WDFY3-AS2, CASC8, UGDH-AS1, RAP2C-AS1, AC007128.1, AC016205.1, AC092803.2 and AC079949.2) were correlated with overall survival of the patients with ESCA. The key differentially expressed genes participate in the development and progression of ESCA, and thus the elucidation of functions of lncRNA-miRNA-mRNA will provide new novel therapeutic target for the patients with ESCA.