METTL3 is significantly downregulated in human sorafenib-resistant hepatocellular carcinoma, whereas METTL3 depletion markedly enhances FOXO3 mRNA stability and eliminates METTL3 mediated sensitivity to sorafenib m6A dependence, which could restore resistance to HCC if FOXO3 overexpression was present. This evidence concerns the gene FOXO3 and hepatocellular carcinoma.