Intriguingly, mass spectrum and in vitro O-GlcNAcylation assay indicate that FH is O-GlcNAcylated by OGT at Ser 75; and cancer cells exhibit high FH O-GlcNAcylation levels along with a strong OGT activity, which soundly impairs AMPK-mediated FH phosphorylation and the relevant cellular sensitivity to the low glucose availability. This evidence concerns the gene FH and cancer.