Objective To analyze the influencing factors of prognosis of patients with traumatic brain injury (TBI), and explore the influence of hemoglobin (Hb) level combined with blood pressure variability (BPV) on the quality of prognosis of patients with TBI. Methods The data of 186 TBI patients who received systemic treatment in the Affiliated Zhangjiagang Hospital of Soochow University between January 2020 and December 2021 were retrospectively analyzed. According to the Glasgow Outcome Scale (GOS) 3 months after treatment, they were divided into group A (GOS 4-5, 159 cases) and group B (GOS 1-3, 27 cases). The general clinical data, BPV indexes and Hb levels of the two groups were analyzed by single factor analysis and multiple logistic regression analysis, and the predictive value of the logistic regression model was evaluated by receiver operating characteristic (ROC) curve, sensitivity, specificity and area under the curve (AUC). Results There was no statistical significance in gender, age, body mass index, blood urea nitrogen, prothrombin time, fasting blood glucose level, or smoking history (P>0.05); the patients’ Glasgow Coma Scale at admission in group A was higher than that in group B (P<0.05), and the constituent ratio with a history of hypertension of group A was significantly lower than that of group B (P<0.05). The between-group differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and Hb at admission, and SBP, DBP, and MAP 72 h after treatment were not statistically significant (P>0.05); the SBP-standard deviation (SD), DBP-SD, SPB-coefficient of variation (CV) and DBP-CV of group B 72 h after treatment were significantly higher than those of group A (P<0.05), and the level of Hb was significantly lower than that of group A (P<0.05). Hb [odds ratio (OR)=0.787, 95% confidence interval (CI) (0.633, 0.978), P=0.031], SBP-CV [OR=1.756, 95%CI (1.073, 2.880), P=0.023] and DBP-CV [OR=1.717, 95%CI (1.107, 2.665), P=0.016] were all independent prognostic factors of TBI patients. The ROC showed that the combined index of BPV and Hb was more valuable than that of single prediction, with an AUC of 0.896 [95%CI (0.825, 0.935), P<0.05]. Conclusions Both BPV and Hb are independent factors affecting the prognosis of TBI patients, and their combined application can more effectively predict the prognosis of TBI patients. Therefore, when treating and evaluating the prognosis of TBI patients, closely monitoring the changes in blood pressure and Hb levels can timely and effectively control the development of the disease, and provide scientific reference for subsequent treatment.