Objective To explorethe mechanism and down stream signaling pathways of ZNF185 in esophageal squamous cell carcinoma by transcriptome sequencing and bioinformatics analysis. Methods The expression of ZNF185 was knocked down by conducting shRNA transfection of esophageal squamous carcinoma cell lines,and the changes of mRNA expression were detected by transcriptome sequencing technology. The differential genes were screened based on sequencing data,and the differential gene-related functions and signaling pathways were analyzed by GO functional analysis and KEGG enrichment analysis. The interactions of differential proteins were analyzed by STRING,and the related protein-protein interaction(PPI) network was constructed to analyze the keynode proteins. Results There were 3859 differential genes between shZNF185 group and the control group,including 2112 genes with elevated expressionand 1747 genes with decreased expression. RNA splicing cell-matrix junction,local adhesion were significantly enriched in GO analysis. KEGG enrichment analysis indicated that ZNF185 might be related to HIF-1 signaling pathwayand p53 signaling pathway,and key proteins such as BMP2 and OAS2 were identified in PPI network. Conclusion The possible signaling pathways involved in the regulation of esophageal squamous carcinoma by ZNF185 werescreened out by transcriptome sequencing and bioinformatic analysis, which provide a newidea to elucidate the pathogenesis associated with esophageal squamous carcinoma.