Mechanistically, ZFP91 promoted the Lys48-linked ubiquitination of the oncoprotein hnRNP A1 at lysine 8 and proteasomal degradation, thereby inhibiting hnRNP A1-dependent PKM splicing, subsequently resulting in higher PKM1 isoform formation and lower PKM2 isoform formation and suppressing HCC glucose metabolism reprogramming, cell proliferation and metastasis. Here, PKM is linked to hepatocellular carcinoma.