ZFP91 interacted with hnRNP A1 and Lys48-ubiquitinated hnRNP A1 at Lys 8 to promote proteasomal degradation of hnRNP A1, thereby inhibiting hnRNP A1-dependent PKM mRNA pre-mRNA splicing to induce PKM1 isoform formation and inhibit PKM2 isoform formation and HCC metabolism reprogramming. This evidence concerns the gene PKM and hepatocellular carcinoma.