Objective To investigate the expression of HIF-1α and the relationship between HIF-1α and P53，Bcl-2 in immature brain after hypoxia ischemia brain damage. Methods Postnatal day 7 SD rats were divided into three groups: sham group, the hypoxia group and the hypoxia-ischemia group. Rats were collected at 3h, 6h, 12h, 24h and 72h after hypoxia or hypoxia ischemia from each group. HE staining was used to detect histopathological damage. Immunohistochemistry was used to detect the expression of HIF-1α, P53 and Bcl-2. Results HE staining showed that neuronal degeneration and edema became prominent at 24h after hypoxia and hypoxia ischemia. The expression of HIF-1α protein was significantly upregulated at 3h, peak at 12h, and then decreased after hypoxia and hypoxia ischemia in both hypoxia and hypoxia ischemia group. The expression of P53 protein was upregulated at 3h, peak at 24h, and then decreased after hypoxia and hypoxia ischemia in the two groups. The expression of Bcl-2 protein was similar with HIF-1α in both groups. The rate of P53 and Bcl-2 was almost 1 in sham group, less than 1 at 3h, 6h and 12h in both hypoxia and hypoxia ischemia groups, and more than 1 at 24h and 72h in both hypoxia and hypoxia ischemia groups. Conclusion The HIF-1α participates in the regulation of P53 and Bcl-2 in immature brain after hypoxia ischemia brain damage. HIF-1α may have protective role in the onset of hypoxia.