OBJECTIVE： To explore clinical efficacy and safety of Ulinastatin injection combined with Xingnaojing injection in the treament of severe craniocerebral injury （CCI）. METHODS： A total of 120 severe CCI patients selected from our hospital during Sept. 2014-Nov. 2015 were divided into ulinastatin group， Xingnaojing group and combination group according to therapy plan， with 40 cases in each group. Three groups were given routine treatment timely after admission. On the basis of routine treatment，  Ulinastatin group additionally received Ulinastatin injection 200 000 U， ivgtt， bid； Xingnaojing group additionally received Xingnaojing injection 20 mL， ivgtt， qd； combination group additionally received Ulinastatin injection combined with Xingnaojing injection， same usage as above （with 1 h intervals）. Three groups received therapy for consecutive 14 d. Serum inflammatory factors （CRP， IL-1， IL-6， TNF-α）， serologic indexes of craniocerebral injury [neuron specific enolase （NSE）， myelin basic protein （MBP）， S100B protein （S100B）] and GCS scores before and after treatment as well as GOS scores after treatment were all observed in 3 groups. The occurrence of ADR was recorded during treatment. RESULTS： Before treatment， there was no statistical significance in serum inflammatory factors， serologic indexes of craniocerebral injury or GCS scores among 3 groups （P＞0.05）. Compared to before treatment， inflammatory factors of 3 groups were decreased significantly after treatment， the ulinastatin group was significantly lower than the Xingnaojing group， combination group was significantly lower than two single drug groups， with statistical significance （P＜0.05）. Levels of serologic indexes of craniocerebral injury and GCS scores of 3 groups were improved significantly， and the combination group was significantly better than the two single drug groups， with statistical significance （P＜0.05）. There was no statistical significance between ulinastatin group and Xingnaojing group （P＞0.05）. Six months after treatment， GOS score of combination group（4.17±0.81）was significantly better than those of ulinastatin group （3.05±0.97） and Xingnaojing group （2.97±0.89）， with statistical significance （P＜0.05）； there was no statistical significance between ulinastatin group and Xingnaojing group （P＞0.05）. During treatment， the incidence of ADR in combination group （27.50％） was significantly lower than ulinastatin group （50.00％） and Xingnaojing group （42.50％）， with statistical significance （P＜0.05）； there was no statistical significance between ulinastatin group and Xingnaojing group （P＞0.05）. CONCLUSIONS： Ulinastatin injection combined with Xingnaojing injection can significantly decrease serum inflammatory factor levels， relieve craniocerebral injury， protect cerebral tissue and improve short-term prognosis with good safety.