Objective To investigate the effect of stress-induced hyperglycemia on the prognosis of the patients after operation for severe craniocerebral injury. Methods A retrospective study was conducted on the patients with severe craniocerebral injury confirmed by radiological imaging and Glasgow Coma score (GCS score, 3 to 8 points), who were admitted to our hospital from January 2016 to December 2018. After surgical treatment, all the patients were transferred to the intensive care unit (ICU) for further treatment, and were divided into normoglycemia group, stressinduced hyperglycemia group and diabetes mellitus group. The 28-day mortality, length of ICU stay, and complications were compared among the three groups. SPSS statistics 16.0 was used to perform the statistical analysis. Data were expressed as mean±standard deviation (±s), median and interquartile range [M(Q₁, Q₃)], or number of cases (percentage). According to the data type, one-way analysis of variance, SNK-q test, Kruskal-Waills rank sum test, Chi-square test or Fisher exact probability test were employed for comparison. Survival data were analyzed using Kaplan-Meier method to draw survival curves, and intergroup comparison of survival rates was performed using Log-rank test. Cox regression model was applied to analyze the risk factors affecting prognosis. Results A total of 165 patients were enrolled, with 55 in each group. Kaplan-Meier survival analysis showed that the 28-day cumulative survival rate was significantly lower in the stress-induced hyperglycemia group than thenormoglycemia group and the diabetes mellitus group. The 28-day mortality rate was obviously higher in the stress-induced hyperglycemia group [43.27%, (26/55)] followed by the diabetes mellitus group [23.64%, (13/55)] and the normoglycemia group [18.18%, (10/55)] sequentially. The mortality of the stress-induced hyperglycemia group was significantly higher than those of the other 2 groups (both P<0.05). But no such difference was seen between the normoglycemia group and the diabetes mellitus group (P>0.05). The incidence of pulmonary infection within 4 weeks were notably higher in the stress-induced hyperglycemia group than the normoglycemia group [58.18%(32/55) vs 34.55%(19/55), P<0.05], and was higher than the diabetes mellitus group [49.10%(27/55)], but the difference was not statistically significant (P>0.05). There were no remarkable differences in the incidences of complications, such as intracranial infection, secondary cerebral infarction, deep venous thrombosis of the lower extremity, acute renal failure and ICU stay length among the 3 groups (P>0.05). Multivariate Cox proportional hazard regression analysis showed that stress-induced hyperglycemia was one of the risk factors affecting prognosis (HR=1.16,95%CI:1.07-1.26). Conclusion The 28-day mortality rate is significantly higher in the patients with severe craniocerebral injury complicated with stress-induced hyperglycemia than those with normoglycemia and diabetes history, suggesting that stress-induced hyperglycemia is a risk factor for prognosis.