We evaluated the performance of arterial spin-labeled perfusion imaging and diffusion-weighted imaging in diagnosing full-term neonatal hypoxic-ischemic encephalopathy. Arterial spin-labeled, diffusion-weighted imaging and conventional magnetic resonance imaging (T1-weighted imaging, T2-weighted imaging and T2 fluid-attenuated inversion recovery) were performed in 23 full-term neonates with hypoxic-ischemic encephalopathy group 10 normal neonates (Control group). The cerebral blood flow and the apparent diffusion coefficient were measured in the bilateral basal ganglia, thalamus and frontal white matter. The effect of neonatal age on the CBF and apparent diffusion coefficient values were further investigated after dividing the 23 ischemic encephalopathy cases into three subgroups (1–3 days, 4–7 days, and 8–15 days). The cerebral blood flow values in the thalamus and lenticular nucleus were significantly higher. The apparent diffusion coefficient values in the thalamus, frontal white matter and lenticular nucleus head were significantly lower in the hypoxic-ischemic encephalopathy group than those in the Control group (p 0.05). There were no significant differences between the ischemic encephalopathy and Control groups in the cerebral blood flow values in the caudate nucleus head and frontal lobe white matter (p > 0.05). The cerebral blood flow and apparent diffusion coefficient values in the thalamus and lenticular nucleus were negatively correlated. Comparison among different age subgroups of hypoxic-ischemic encephalopathyneonates showed that the cerebral blood flow value was higher. In comparison, the apparent diffusion coefficient value was lower in the 1–3 days old neonates than those in the older neonates (p 0.05). Arterial spin-labeled and diffusion-weighted imaging could reflect the ischemic encephalopathy pathological processes more comprehensively. The cerebral blood flow measurement and apparent diffusion coefficient values in the thalamus and the lenticular nucleus may represent a novel way to diagnose ischemic encephalopathy early.