The mechanisms underlying hypoxia-induced HCC cells escape from sorafenib include HIF-mediated metabolic reprogramming [104], regulation of the PI3K/AKT signaling pathway [105], etc. The above-mentioned study on SOX9 further expands the mechanism of hypoxia-induced sorafenib resistance and closely links hypoxia, CSCs, and sorafenib sensitivity. The gene discussed is SOX9; the disease is hepatocellular carcinoma.