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. The gene discussed is MTDH; the disease is hepatocellular carcinoma.