The results of the current study demonstrated for the first time that VitD restores EVE sensitivity in HCC cells, which had acquired resistance to EVE, through different mechanisms, involving the control of EMT and the regulation of several oncogenes, including MTDH, YAP-1 and c-MYC, by means of the activation of miR-375. This evidence concerns the gene YAP1 and hepatocellular carcinoma.