Background: Although diagnostic methods and treatments have improved over the last few years, the 5-year survival rate of esophageal squamous cell carcinoma (ESCC) patients remains generally poor. The development of high-throughput technology has facilitated great achievements in localization of ESCCrelated genes. To take a further step toward a thorough understanding of ESCC at a molecular level, the potential pathogenesis of ESCC needs to be deciphered.Methods: The interaction of ESCC-related genes was explored by collecting genes associated with ESCC and then performing gene enrichment assays, pathway enrichment assays, pathway crosstalk analysis, and extraction of ESCC-specific subnetwork to describe the relevant biochemical processes.Results: Through Gene Ontology (GO) enrichment analysis, many molecular functions related to response to chemical, cellular response to stimulus, and cell proliferation were found to be significantly enriched in ESCC-related genes. The results of pathway and pathway crosstalk analysis showed that pathways associated with multiple malignant tumors, the immune system, and metabolic processes were significantly enriched in ESCC-related genes. Through the analysis of specific subnetworks, we obtained some novel ESCC-related potential genes, such as MUC13, GSTO1, FIN, GRB2, CDC25C, and others.Conclusions: The molecular mechanism of ESCC is extremely complex. Some inducing factors change the expression status of many genes. The abnormal expression of genes mediates the biological processes involved in immunity and metabolism, apoptosis, and cell proliferation, leading to the occurrence of tumors. The genes MUC13, RYK, and FIN may be potential prognostic indicators of ESCC; GRB2 and CDC25C may be potential targets of ESCC in proliferation. Our work may provide valuable information for further understanding the molecular mechanisms for the development of ESCC.