The combination of sorafenib and EF24, a curcumin analog, can overcome hypoxia-mediated sorafenib resistance by encouraging the proteasomal degradation of HIF-1α in a VHL-dependent manner in HCC cells, leading to the suppression of its target genes MDR1, GLUT-1, and VEGF and activity of NF-κB. The gene discussed is HIF1A; the disease is hepatocellular carcinoma.