OBJECTIVE： To investigate the clinical efficacy and safety of amoxicillin sodium and clavulanate potassium combined with cranial mild-moderate hypothermia in the treatment of neonatal hypoxic-ischemic encephalopathy （HIE） complicating with pulmonary infection. METHODS： 80 children with HIE complicating with pulmonary infection were randomly divided into observation group （42 cases） and control group （38 cases）. Control group received routine treatment under normal body temperature as lowering intracranial pressure， correcting acid-base balance， giving nutritional support and anticonvulsive treatment， and then was given amoxicillin sodium and clavulanate potassium 30 mg/kg intravenously， tid， more than 30 min each time， for consecutive 3 d. On the basis of control group， observation group was additionally given cranial mild-moderate hypothermia therapy： wearing cooling cap， at 10 ℃； keeping pharynx nasalis temperature at 34 ℃； keeping rectal temperature at 33-37 ℃； decreasing at rate of 1 ℃/h. They continued treatment for 3 d till body temperature decreased to 34.5 ℃； and then cooling cap was taken off to recover normal body temperature. Therapeutic efficacy of HIE and pulmonary infection were observed in 2 groups. NBNA score of 2 groups were recorded 1st， 2nd and 4th week after birth， and the occurrence of ADR was observed. RESULTS： Total effective rate of HIE therapy （95.24％ vs. 78.95％）， cure rate of pulmonary infection （52.38％ vs. 26.32％） and total effective rate （85.71％ vs. 65.79％） in observation group were significantly higher than control group， with statistical significance （P＜0.05）. There was no statistical significance in NBNA score between 2 groups 1st week after birth （P＞0.05）. Compared to 1st week after birth， NBNA score were significantly improved 2nd and 4th week after birth， and the observation group were significantly higher than the control group， with statistical significance （P＜0.05）. There was no statistical significance in the incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： Amoxicillin sodium and clavulanate potassium combined with cranial mild-moderate hypothermia is effective for HIE complicating with pulmonary infection， and can effectively improve the prognosis of children with good safety.