Tumor recurrence and metastasis after surgery are the leading causes of death in patients with esophageal squamous cell carcinoma (ESCC). Next-generation sequencing techniques have improved our understanding of the genetic alterations underlying tumor initiation and progression. To explore recurrence-specific transcriptional profiles, functional properties, and gene co-expression networks in ESCC, samples from recurrence (n = 4) and nonrecurrence (n = 4) groups were analyzed by RNA sequencing. Patients included in the nonrecurrence group had five or more years of survival without any evidence of recurrence or metastasis, while those included in the recurrence group exhibited early recurrence and metastasis and died within 2 years. We identified 533 significantly differentially expressed protein-coding and noncoding genes. Functional enrichment analysis indicated that ESCC recurrence was related to dysregulated cell-cell adherence, microenvironment homeostasis, information processing, and the immune response. Co-expression networks demonstrated differences in the patterns of gene expression and co-expression between the recurrence and nonrecurrence groups. This study provided important insights into ESCC progression and the differentially expressed genes that may represent potential targets for ESCC diagnosis and therapy.