VEZF1 is stabilized by GFAT1-mediated O-GlcNAcylation, thereby enhancing the binding of VEZF1 to the promoter region of Tensin 1 (TNS1), activating the transcription of TNS1. Our findings reveal that the GFAT1-VEZF1-TNS1 axis plays a key role in regulating HCC progression, and suggest new therapeutic strategies. This evidence concerns the gene TNS1 and hepatocellular carcinoma.