Naloxone as an assist drug has been used to treat neonatal hypoxic ischemic encephalopathy (HIE). However, there is controversy about its therapeutic effect. This study aims to evaluate the effect by Meta analysis. Methods Using the Meta analysis method, 20 case control studies about the effect of naloxone on neonatal HIE were qualitatively and quantitatively analysed, and the combined OR value and 95% confidence interval (CI) of curative effects and side effects were calculated. Results Compared with the routine therapy, the therapy with naloxone can significantly improve clinical symptoms of neonates with HIE(combined OR= 4.89 , 95% CI= 2.59 - 9.21 ). Also, it can significantly shorten the time of respiratory failure (combined OR= 11.09 , 95% CI= 5.13 - 23.98 ), gastro intestine function failure (combined OR= 44.58 , 95% CI= 18.42 - 107.93 ) and circulatory system dysfunction (combined OR= 5.54 , 95% CI= 2.97 - 10.35 ), and increase the survival rate (combined OR= 3.38 , 95% CI 2.01 - 5.71 ). Conclusions The therapy with naloxone can markedly improve the severity and increase the survival rate of neonates with HIE.