OBJECTIVE: This study aims to investigate the application value of three-dimensional arterial spin labeling (ASL) perfusion imaging in detecting cerebral hemodynamics of neonates with hypoxic-ischemic encephalopathy (HIE). METHODS: Sixty normal full-term neonates and 60 HIE neonates were enrolled in this study and were respectively divided into three groups: the 1-3 days group, the 4-7 days group, and the 8-15 days group. The brains of these neonates were scanned with the 3D ASL sequence, and cerebral blood flow (CBF) images were obtained. The CBF values of the bilateral symmetrical brain regions and brain stem were measured on CBF images, and the values were averaged. The cerebral blood flow of HIE neonates in the 1-3 days group, the 4-7 days group, and the 8-15 days group was compared with normal neonates at matched ages, and the characteristics of cerebral hemodynamics in HIE neonates at different ages were summarized. RESULTS: The CBF values of the basal ganglia, thalamus, and brainstem in the 1-3 days HIE group were higher than normal neonates at matched ages, and the CBF value of the frontal lobe was lower than the normal group, and the differences were statistically significant (P < 0.05). The CBF values of the basal ganglia, thalamus, corona radiata, and frontal lobe in the 4-7 days HIE group were lower than the normal group, and the differences were statistically significant (P < 0.05). There were no significant differences in CBF values of different brain regions between the 8-15 days HIE and normal groups (P > 0.05). CONCLUSION: Early hyperperfusion of the basal ganglia and thalamus is helpful for early diagnosis and prognosis of HIE.