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During neonatal hypoxic–ischemic brain injury, activation of transcription of a series of genes is induced to stimulate erythropoiesis, anti-apoptosis, apoptosis, necrosis and angiogenesis. A key factor mediating these gene transcriptions is hypoxia-inducible factor-1α (HIF-1α). During hypoxia, HIF-1α protein is stabilized and heterodimerizes with HIF-1β to form HIF-1, subsequently regulating the expression of target genes. HIF-1α participates in early brain development and proliferation of neuronal precursor cells. Under pathological conditions, HIF-1α is known to play an important role in neonatal hypoxic–ischemic brain injury: on the one hand, HIF-1α has neuroprotective effects whereas it can also have neurotoxic effects. HIF-1α regulates the transcription of erythropoietin (EPO), which induces several pathways associated with neuroprotection. HIF-1α also promotes the expression of vascular endothelial cell …