Regional cerebral oxygen saturation (rScO2) monitoring can reflect the oxygenation of local brain tissue in real time, continuously and non‑invasively. Although most studies showed negative effects of one⁃lung ventilation (OLV) on rScO2 which correlated with an increased incidence of perioperative neurocognitive disorders (PND), some investigators demonstrated that the relatively decreases of rScO2 were highly dependent upon what the baseline conditions were, and the current definition of low rScO2 is still unclear. Also, a lack of clear definition of cerebral desaturation was considered a major contributing factor to the discrepancies between the related studies. This review will summarize the changes of rScO2 and its influencing factors during OLV, the occurrence of PND in OLV patients, and the controversies and limitations of related studies on OLV and rScO2 changes. The numerous application of rScO2 monitoring still needs in‑depth research and exploration. It is believed that with more experience acquired in clinical use, rScO2 is expected to provide more non⁃cerebral information to improve patients' outcome.