Objective To investigate the value of serum copeptin and insulin-like growth factor-II （IGF-II） combined with Acute Physiology and Chronic Health Evaluation II （APACHE II） score in predicting the prognosis of patients with traumatic brain injury.Methods A total of 96 patients with traumatic brain injury who attended our hospital from December 1， 2012 to December 1， 2018 were enrolled as experimental group， and 96 healthy individuals were enrolled as control group. The serum levels of copeptin and IGF-II were measured for all subjects. The prognosis of the patients in the experimental group were evaluated， and the serum levels of copeptin and IGF-II were analyzed for patients with different prognoses.Results After admission， the experimental group had a gradual reduction in the serum level of copeptin and a gradual increase in the serum level of IGF-II. There were significant differences in the serum levels of copeptin and IGF-II between the mild group， the moderate group， and the severe group （P <0.05）； compared with the moderate group， the mild group had a higher level of IGF-II and a lower level of copeptin， and compared with the severe group， the moderate group had a higher level of IGF-II and a lower level of copeptin. APACHE II score was positively correlated with copeptin level and negatively correlated with serum IGF-II level. For the patients in the experimental group at 6 months after discharge， the worse the prognosis， the higher the serum level of copeptin and the lower the serum level of IGF-II on admission.Conclusions Serum levels of copeptin and IGF-II combined with APACHE II score have a certain value in predicting the prognosis of patients with traumatic brain injury.