Objective To evaluate the effect of driving pressure⁃guided individualized positive end⁃expira⁃ tory pressure（PEEP）on intracranial pressure and regional cerebral oxygen saturation（rSO2）in elderly patients undergoing robot ⁃ assisted laparoscopic radical prostatectomy（RALP）. Methods Eighty patients with elective general anesthesia for RALP，aged 65 to 80 years，with BMI 19 to 28 kg/m2 ，and ASA classification I to Ⅲ，were selected. A randomized number table method was used to divide the patients into conventional pulmonary protective ventilation（group A）and individualized PEEP with driving pressure guidance（group B）. In group A，5 cmH20 PEEP was fixed 10 minutes after the Trendelenburg position was adjusted for low tidal volume lung protection venti⁃ lation；In group B，PEEP titration was performed after the establishment of pneumoperitoneum position and supine position. The air was ventilated with the PEEP until the tracheal tube was removed. The mean arterial pressure （MAP）was recorded immediately before anesthesia induction（T0），5 minutes after endotracheal intubation（T1）， 5 minutes after CO2 pneumoperitoneum establishment（T2），5 minutes after pneumoperitoneum Trendelenburg position（T3），5 minutes after positive end⁃expiratory pressure titration（T4，10 minutes after PEEP ventilation in group A），60 minutes after positive end⁃expiratory pressure titration（T5），and 5 minutes after surgery（T6）. Systolic blood flow velocity（VS），blood flow velocity diastolic period（VD），mean blood flow velocity（VM），and pulsation index（PI）of the middle cerebral artery were measured，and cerebral perfusion pressure（CPP）were calculated； T1⁃6 lung compliance（Cdyn），arterial partial pressure of oxygen（PaO2）and arterial partial pressure of carbon dioxide（PaCO2）and T0 ⁃ 6 rSO2 were recorded；Pulmonary complications were recorded one week after operation. Results Compared with group A，group B had higher Cdyn and PaO2 at T5⁃6 and a significantly lower incidence of pulmonary complications（P < 0.05），with no significant differences in MAP，CPP and SO2 between the two groups （P > 0.05）. Conclusion Individualized PEEP guided by driving pressure in RALP is safe and effective. It can improve the pulmonary oxygenation function and compliance during operation，reduce the incidence of postopera⁃ tive pulmonary complications，and have no significant impact on cerebral hemodynamics and rSO2.