Low-risk group maintained ZHX1, WDYHV1, FBXO32, ATAD2, and PKLR amplifications referring to transcriptional deregulation, TGF-beta1/Smad3 signaling pathway, and oxidative phosphorylation, as well as deletion of tumor suppressor genes CSMD1, ERICH1, MYOM2, and FBXO25. Taken together, genomic analysis across the different risk groups of HCC revealed the mechanisms of tumor progression and helped to identify biomarkers in response to targeted therapies. Here, PKLR is linked to hepatocellular carcinoma.