Aim: The aim of the study was constructing a protein–protein interaction network for chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients. Materials & methods: Comprehensive gene expression profile of peripheral blood mononuclear cells of CHB and HCC were obtained from Gene Expression Omnibus/NCBI database. Differentially expressed genes (DEGs) of samples were analyzed using GEO2R web application. Results: The majority of DEGs in both CHB and HCC has been enriched in immune system responses. However, there was a significant disparity between the enrichment of these genes (especially genes associated with Toll-like receptor-and-TNF) in CHB-HCC compared with normal-CHB. Conclusion: The transcriptome properties of peripheral blood mononuclear cells are changed in patients with HBV-HCC. The immune response genes are the most deregulated genes in HCC patients. [Formula: see text]