ObjectiveTo objectively evaluate the effect and safety of naloxone for the treatment of moderate and severe neonatal hypoxia-ischemic encephalopathy (HIE). MethodsResearch articles published from inception to June 2015 on Cochrane library, PubMed, Web of science, Chinese Science and Technology Journal Full-text Database, Digital Full-text Journal Database and Chinese Journal Full-text Database were searched, which were relevant to naloxone in the treatment of moderate and severe neonatal HIE. And two authors extracted information via standardized data extraction form and assessed the quality of included studies independently. RevMan 5.2 software was used for Meta-analysis. ResultsAt last, 20 randomized controlled trials (involving 1 519 neonates; 783 in the treatment group and 736 in the control group) were included. The results of meta-analysis showed that the effect of naloxone for moderate and severe HIE was significantly superior to the control group[OR=5.07, 95%CI (3.61, 7.12), P < 0.000 01]. The neurobehavioral scores in neonates treated by naloxone after 5, 7, 10, and 14 days were higher than those in the control group[WMD=6.61 points, 95%CI (5.70, 7.51) points, P < 0.000 01; WMD=4.27 points, 95%CI (2.63, 5.91) points, P < 0.000 01; WMD=2.40 points, 95%CI (1.47, 3.34) points, P < 0.000 01; WMD=2.58 points, 95%CI (1.00, 4.16) points, P=0.001], respectively; while the neurobehavioral scores after 3-day treatment between the two groups had no statistically difference[WMD=0.00 points, 95%CI(-0.76, 0.77) points, P=0.99]. What's more, the disappeared time of clinical symptoms and signs (breathing improvement time, recovery time, convulsions disappearance time, and signs disappearance time) in naloxone group was superior to the control groups[WMD=-3.78 hours, 95%CI (-6.93, -0.64) hours, P=0.02; WMD=-9.66 hours, 95%CI (-14.25, -5.06) hours, P < 0.001; WMD=-2.81 hours, 95%CI (-5.28, -0.35) hours, P=0.03; WMD=-1.02 days, 95%CI (-1.84, -0.20) days, P=0.01], respectively. ConclusionsNaloxone has certain therapeutic on moderate and severe HIE. Further high-quality randomized controlled trials should be carried out to provide more reliable evidence.