This study reveals that 1,25(OH)2D3 enhances the chemosensitivity of hepatocellular carcinoma (HCC) to sorafenib, with underlying mechanisms potentially involving the targeted modulation of the FOXO3A/FOXM1 signaling axis and the reversal of sorafenib-resistant phenotypes through the regulation of apoptotic and autophagic pathways. This evidence concerns the gene FOXO3 and hepatocellular carcinoma.