These results suggest that the primary mechanism by which 1,25(OH)2D3 enhances the chemosensitivity of HCC to sorafenib may involve the FOXO3A/FOXM1 axis, regulating the proliferation and apoptosis of drug-resistant cells and the onset of cellular autophagy, thereby playing a role in reversing resistance to sorafenib in HCC. Here, FOXO3 is linked to hepatocellular carcinoma.