Intervertebral disc degeneration (IDD) is one of the main causes of low back pain-a common clinical problem. Alterations of the phenotype, reduction of survival time, decline of metabolic activity, and decrease of extracellular matrix of nucleus pulposus (NP) cells are thought associated with IDD. The intervertebral disc is the largest avascular tissue in the body, with the most distinctive characteristic being low oxygen tension. Hypoxia-inducible factor (HIF) is a transcriptional factor induced by the hypoxia condition to initiate a series of cellular responses, accommodating the hypoxia environment. HIF can start transcription of target genes by binding the hypoxia response element and may play an important role in the pathological process of IDD and serve as a crucial target for stopping progression or curing IDD. Here we summarized the roles of HIF in regulating metabolism activity of NP cells, including expression of HIF in NP cells, and regulatory roles of HIF in phenotype, survival, metabolism and extracellular matrix accumulation of NP cells.