Objective To study the effect of early nursing intervention on the prognosis of neonates with hypoxic-ischemic encephalopathy. Methods From Jun. 2011 to Jun. 2014, a total of 160 neonates with hypoxic-ischemic encephalopathy who accepted treatment in our hospital were taken as the clinical research objects, and these patients were randomly divided into intervention group (80 cases) and control group (80 cases). All of these patients were treated with conventional care. Besides, the intervention group received additional early nursing intervention in order to compare their mental and motor development. Results 6 and 12 months after intervention, the MDI and PDI score in the intervention group were significantly higher than those in the control group (P<0.05), 12 months after intervention, the adaptive ability, gross motor ability, fine motor and language ability of the intervention group were significantly better than those of the control group (P<0.05). Conclusion Early nursing intervention can not only promote the development of intelligence and exercise capacity, but also improve the prognosis of neonates with hypoxic-ischemic encephalopathy.