Our previous study has demonstrated the presence of positive feedback loop between HIF‐1α and SENP1 deSUMOylase which contributes to the maintenance of HCC stemness and tumorigenesis under hypoxia.[8] Here, intriguingly we found that OTUD6B is induced by hypoxia as a direct target of HIF in HCC cells. The gene discussed is OTUD6B; the disease is hepatocellular carcinoma.