The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients. This evidence concerns the gene PBK and hepatocellular carcinoma.