In HCC, TRIM65 was significantly overexpressed via O‐GlcNAcylation by OGT and mediated ubiquitylation of NF2 at the K44 residue toward degradation as an E3 ligase, inhibiting the phosphorylated activation of LATS1/2 resulting in the accumulation of YAP1 in the nucleus, thus promoting the transcription of downstream targets, including CTGF, UMPS and FASN. This evidence concerns the gene TRIM65 and hepatocellular carcinoma.