Objective：To analyze the effect of mild hypothermia combined with ganglioside on moderate and severe neonatal brain injury. Methods：From June 2018 to June 2020，86 newborns with severe brain injury in Zhangzhou Second hospital were randomly divided into observation group and control group，43 cases in each group. The control group was given ganglioside treatment on the basis of routine treatment and ECG monitoring；the observation group was given mild hypothermia treatment on the basis of the control group， and the neurobehavioral tests of the two groups were compared NBNA score，clinical efficacy， muscle tension，reflex，recovery time of consciousness and complications of sequelae. Results： After treatment，the NBNA scores on the third，seventh and fourteenth days of the two groups were increased，and the NBNA scores of the observation group after treatment were significantly higher than those before treatment and the control group （P<0.05）；the total effective rate of the observation group was 95.35%，which was significantly higher than that of the control group（ 81.39%）（ P<0.05）；the recovery time of muscle tension，reflex and consciousness in the observation group was significantly higher than that in the control group （P<0.05） The incidence of cerebral palsy，mental retardation，epilepsy and other sequelae in the observation group were significantly lower than those in the control group （P<0.05）. Conclusion：Mild hypothermia combined with ganglioside can effectively treat moderate and severe neonatal brain injury， improve NBNA score，reduce muscle tension，reflex，consciousness recovery time，and reduce the incidence of sequelae. The clinical effect is good and has high clinical application value.