Oxygen homeostasis is crucial for the maintenance of cell function. Hypoxia-inducible factor (HIF) oxygen-sensing pathway plays an important role in the regulation of oxygen concentration and the maintenance of oxygen homeostasis. The change from hyperoxia to normoxia or from normoxia to hypoxia can put cells in a relatively hypoxic state, and it can trigger the intracellular cascade reaction usually triggered by hypoxia and enhance the ability of cells to resist hypoxia. This phenomenon is called "hyperoxic-hypoxic paradox" (HHP), and its mechanism is related to the up-regulation of HIF-1α induced by HHP. This paper reviews the research progress of HIF oxygen-sensing pathway and HHP.