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Objective To identify the time course of regional cerebral oxygen saturation (rScO2) during laparoscopic surgery with trendelenburg position in gynecology and to quantify the effect of related factors. Methods Data from patients scheduled for elective gynecological laparoscopic surgery were collected and analyzed from June 2017 to Aug 2018 in Peking Union Medical College Hospital. Spline and mixed-effects models were used to investigate the changing trend and affecting factors of rScO2. Results Forty-eight ASA Ⅰ~Ⅱ patients were included. rScO2 presented a U-shaped trend over time with the spline model (P＜0.01 for the non-linear association). Episodes of cerebral deoxygenation were observed in 3 patients during the declining period of rScO2. Mean blood pressure, systolic blood pressure and end-tidal CO2 (ETCO2) were positively associated with rScO2 (P＜0.05). Peak airway pressure (PAP) and body mass index (BMI) were negatively associated with rScO2 (P＜0.05). Compared with other factors, the effects of BMI and ETCO2 on rScO2 were increased significantly over time(P＜0.05). Conclusions During the gynecological laparoscopic surgery with trendelenburg position, rScO2 changes significantly over time. BMI and ETCO2 exhibite greater effects on rScO2, and the effects increase significantly over time.