Objective: To study the cerebral protective effect of mouse nerve growth factor combined with early hypothermia therapy for patients with severe craniocerebral injury and the influence on the inflammatory and stress reaction indexes. Methods: A total of 68 patients with severe craniocerebral injury who were treated in our hospital between May 2012 and February 2016 were collected and then divided into the control group (n=38) who received mild hypothermia therapy and the observation group (n=30) who received mouse nerve growth factor combined with early hypothermia therapy after the treatment and laboratory test results were reviewed. Immediately after admission and after 2 weeks of treatment, automatic biochemical analyzer was used to detect the contents of nerve injury indexes; enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of neurotransmitters and inflammatory factors; RIA method was used to detect the contents of stress hormones. Results: Before treatment, the nerve injury indexes, neurotransmitters, inflammation factors and stress hormones were not statistically different between two groups of patients (P>0.05); after treatment, peripheral blood nerve function indexes MBP, IMA and NSE levels of observation group were lower than those of control group while BDNF level was higher than that of control group patients (P<0.05); peripheral blood peptide neurotransmitters VAP, Dny-A and NPY as well as amino acid neurotransmitters Glu and Asp contents of observation group were lower than those of control group while GABA level was higher than that of control group (P<0.05); serum inflammatory factors CRP, NF-κB and IL-1β contents as well as stress hormones AngⅡ, Cor, CRH and NE contents of observation group were lower than those of control group (P<0.05). Conclusions: Mouse nerve growth factor combined with early hypothermia therapy can protect the brain function and inhibit the systemic inflammatory and stress reaction in patients with severe craniocerebral injury.