SummaryTo investigate how host cells respond to the hijacking of host cells by Listeria monocytogenes (LM) and affect their gene expression in the process of infection by LM. In this study, three data lines in the GEO database were used for differential expression analysis. The results showed that 34 co-expressed genes (DEGs) were selected from the differential expression analysis of three data lines. Among them, 30 genes were co-up-regulated and 4 genes were co-down-regulated. In the blood test group, 131 genes were up-regulated and 28 genes were down-regulated. In the liver, 132 genes were up-regulated and 18 genes were down-regulated. In the spleen, 142 genes were up-regulated and 11 genes were down-regulated. Among the 30 upregulated IDEGs, GBP3, MB21D1, FPR2, SAMHD1, CXCL10, STAT2, IRF1, and STAT1 genes were involved in the defense response to the virus, type i interferon signaling pathway, and inflammatory response. Functional enrichment analysis revealed that 30 up-regulated genes were enriched in cytoplasmic spermatoproteasome complex, proteasome core complex, and cell membrane lateral signaling pathway, which were involved in the regulation of threonine-type endopeptidase activity and guanosine triphosphate (GTP) signaling process.