Objective To evaluate the clinical efficacy and safety of naloxone hydrochloride in the treatment of severe traumatic brain injury in mild hypothermia environment.Methods A total of 162 cases with severe traumatic brain injury were randomly divided into control group (n =81 cases) and treatment group (n =81 cases).Control group was given conventional therapy and mild hypothermia treatment.On the basis of control group,treatment group was received naloxone hydrochloride injection 0.3 mg · kg-1 · d-1,continued intravenous infusion,qd.Two groups were both treated for 7 d.The levels of serum matrix metalloproteinase-9 (MMP-9) and S100 calcium-binding protein (S100-B),clinical efficacy and safety were compared in two groups.Results After treatment,the total effective rates in treatment group and control group were 82.72％ (67/81 cases),67.91％ (55/81 cases),with significant difference (P ＜ 0.05).After treatment,serum MMP-9 were (38.64 ±5.42),(24.48 ±3.41) μg · mL-1 in control group and treatment group;serum S100-B were (0.98 ± 0.14),and (0.15 ± 0.05) μg · L-1 in control group and treatment group.There was statistically significant difference between two groups (P ＜ 0.05).The adverse drug reactions including gastrointestinal reactions,liver and renal dysfunction in control and treatment groups,the incidence were 11.11％ (9/81 cases) and 7.41％ (6/81 cases),respectively,without significant difference (P ＞ 0.05).Conclusion The treatment of naloxone hydrochloride can significantly reduce the levels of serum MMP-9 and S100-B in patients with severe traumatic brain injury in mild hypothermia environment,and improve clinical efficacy with high safety.