Apoptosis is one of main types of neural cell death and is reversible and is a major target of therapeuticinterventions. However, detailed apoptotic cascades still need to be recognized. In present study, we determined thepromotion of HIF-1α and survivin in brain samples of a mouse model of hypoxic-ischemia and in neuroblastomaSH-SY5Y cells post hypoxia treatment. Then gain-of-function and loss-of-function strategies were adopted tomanipulate the HIF-1α in SH-SY5Y cells, and hypoxia-induced survivin upregulation and cell apoptosis weredetermined. Results demonstrated that the HIF-1α and survivin were significantly promoted in a mouse modelof hypoxic-ischemia or in SH-SY5Y cells post hypoxia in vitro. Manually upregulated HIF-1α could promote thehypoxia-induced survivin upregulation and improve the hypoxia-induced SH-SY5Y cell apoptosis. On the otherhand, the HIF-1α knockdown by RNAi reduced the hypoxia-induced survivin upregulation and cell apoptosis.Therefore, the present study confirmed the protective role of HIF-1α and survivin in the hypoxia-induced SHSY5Ycell apoptosis, and the survivin upregulation by hypoxia is HIF-1α-dependent. Promotion of HIF-1α andsurvivin might be a valuable stragegy for therapeutic intervention for hypoxic-ischemic encephalopathy.