To further investigate the potential manifestation of the METTL3/FOXO3 axis in the in vivo model of HCC with sorafenib treatment, we have used four different mouse models, including the subcutaneous tumor mouse model, the orthotopic liver tumor xenograft mouse model, the human liver cancer PDX model, and the syngeneic xenograft mouse model to mimic the liver microenvironment and to examine the effects of METTL3 depletion on sorafenib treatment. This evidence concerns the gene METTL3 and liver cancer.