<p>Liver Hepatocellular Carcinoma (LIHC) is characterized by complex molecular interplay. Bacterial response-related genes have recently emerged as potential players in the tumorigenic process. In this study, we employed an informatics approach to uncover the role of bacterial response-related genes in LIHC and identify key hub genes and pathways associated with the disease. Initially, the gene expression data of LIHC was downloaded using the TCGAbiolinks package in R and normalized the data while extracting differentially expressed genes (DEGs) using the edgeR and DESeq2 packages. Additional 611 bacterial response-related genes, curated from existing literature, were integrated into the analysis. Venn diagram analysis was used to depict the identified common genes between the DEGs and bacterial response-related genes, shedding light on potential convergence points. Functional enrichment analysis was performed using the Enrichr software, highlighting significant pathways including Neutrophil Extracellular Trap Formation (KEGG), Immune System and Innate Immune System (Reactome). We elucidated protein-protein interactions (PPIs) among the identified genes using STRING, and the resultant network was visualized using Cytoscape. Notably, hub genes were pinpointed using the CytoHubba plugin, showcasing the diagnostic importance of TNF, IL1B, CD4, IL6, IL10, TLR2, and TLR4 in LIHC.</p><p>Collectively, our study presents a comprehensive insight into the molecular landscape of LIHC by integrating bacterial response-related genes. The highlighted hub genes and pathways offer potential avenues for further research and therapeutic intervention in LIHC treatment and management.</p>