Objective To explore the clinical value of target-oriented therapy of monitoring regional cerebral oxygen saturation (rScO₂) in the elderly patients with severe traumatic brain injury (sTBI). Methods A total of 60 patients aged over 60 years with severe craniocerebral injury treated in the neurosurgical intensive care unit (NSICU) of our hospital from April 2018 to November 2020 were enrolled, and then randomly divided into study group and control group, with 30 patients in each group. The control group was given traditional neurosurgical intensive care management, and the study group was given targeted therapy under the direction of monitoring rScO₂ on the basis of conventional neurosurgical intensive care management. Glasgow coma score (GCS) and Glasgow outcome score (GOS), NSICU length of stay, mortality, and modified Rankin scale scores were compared between two groups. SPSS statistics 24.0 was used to perform the statistical analysis. Student′s t test or Chi-square test was employed for intergroup comparison based on different data types. Kaplan-Meier survival curve was used for survival analysis. Results At discharge, the Glasgow coma score (GCS) was increased than that at admission in both groups, but no statistical difference was observed between them (P>0.05), though the score in the study group higher than that of control group (P>0.05). The length of stay in NSICU was significantly shorter in the study group than the control group (P<0.05). After 6 months of follow-up, the study group had obviously lower score of Modified Rankin Scale (mRS), higher GOS, longer survival time and lower mortality when compared with the control group (all P<0.05). Conclusion The targeted therapy under the direction of monitoring rScO₂ can effectively shorten the length of NSICU stay, improve the prognosis and reduce the mortality rate in the elderly sTBI patients.