Objective: To explore the effect of mild hypothermia intervention on the nerve injury as well as neurotransmitters and inflammatory mediators in patients with acute craniocerebral injury. Methods:700 patients with acute craniocerebral injury who were treated in Lueyang People’s Hospital between March 2014 and March 2017 were collected and divided into routine group (n=350) and mild hypothermia group (n=350) by random number table. Routine group accepted craniotomy evacuation of hematoma, and mild hypothermia group accepted mild hypothermia intervention on the basis of craniotomy evacuation of hematoma. The differences in the serum contents of nerve injury-related indexes, amino acid neurotransmitters and inflammatory mediators were compared between the two groups before and after treatment. Results: Before treatment, there was no statistically significant difference in the serum levels of nerve injury-related indexes, amino acid neurotransmitters and inflammatory mediators between the two groups. After treatment, serum nerve injury-related indexes NSE, S100B, Nogo-A and MBP levels of mild hypothermia group were lower than those of routine group; serum amino acid neurotransmitters Asp and Glu levels of mild hypothermia group were lower than those of routine group while GABA level was higher than that of routine group; serum inflammatory mediators HMGB1, IL-8 and TNF-α levels of mild hypothermia group were lower than those of routine group. Conclusion: Early mild hypothermia intervention can effectively relieve the nerve injury in patients with acute craniocerebral injury and exert positive neuroprotective effect.