Hypoxia is a microenvironment that occurs when the oxygen supply is insufficient to perform physiological functions. HIF-1 is a transcriptional factor that mediates metabolisms and cellular responses under hypoxic conditions, which protects the cell’s viability. Harness of the HIF-1α pathway gives control over cellular response and cells’ differentiation directions. In this review article, the degradation process of HIF-1α will be firstly be discussed. It has been proved that the activation and suppression of HIF-1α pathway can stimulate many cellular responses in human body, for instance, chondrogenesis and angiogenesis. Three clinical applications of HIF-1α will be analyzed in this article, which are cartilage repairments, recovery of anemia and the cancer treatment. The upregulation of HIF-1α activates the transcription of many genes responsible for cell proliferation, and this can be achieved by small biomaterial. This method is more controllable in terms of its mechanism, and more commercially available compared with gene therapy approaches and recombinant tissues.