Abstract: Objective: To investigate the curative effect of naloxone in treatment of neonates with middle or severe hypoxic-ischemic encephalopathy (HIE). Methods: Based on the traditional therapy, naloxone was added to treat 20 neonates with middle or severe HIE and compared the curative effect with 12 controls. The indexes included vital signs, resumption time of consciousness, reflex and muscular tension, sustaining time of main symptoms and signs, and curative outcome. Results: Compared with controls, patients treated with naloxone showed better vital signs, their resumption time of consciousness and muscular tension were shoter, as well as their sustaining time of main symptoms and signs. Total effective rate of management group was higher than control group (P=0.030). Conclusions: Naloxone plays an important role in treating neonates with middle or severe HIE, elevates curative effect and has no side effects.