Objective To evaluate the protective effects a potential mechanisms of quercitin. Methods Following isolating neurons from E18 rat fetuses， we used an in vitro model of ischemic injury via oxygen and glucose deprivation（OGD） of cultured neurons. The OGD protocol was commenced by changing the culture medium to low-glucose HBSS and hypoxia condition at 37 ℃ for 3 h. For control cells that did not undergo OGD， the culture medium was replaced with regular glucose-containing culture medium and the neurons were grown under normal oxygen conditions. Following the OGD of cortical neurons， we measured cell viability（CCK-8） and cytotoxicity（LDH）， and explored the potential mechanisms underlying the action of quercitin by integrating ROS and ATP. Results The 3-h OGD induced a significant decrease in cell viability and quercitin treatment induced a dose-dependent improvement in cell viability（P<0.01 at quercitin 25 μM） and decreased neuronal injuries characterized by the breakage of neuronal fibers and shrunken somas； the LDH assay indicated that there was a significant decrease in cytotoxicity following quercitin treatment（P<0.05 at quercitin 25 μM）. ROS levels were greatly increased in neurons subjected to OGD； however， this OGD-induced excessive ROS production was significantly reversed by quercitin（P<0.001 at 25 and 12.5 μM and P<0.05 at 6.25 μM）. ATP production was markedly declined following the 3-h OGD， but quercitin significantly increased ATP levels， seemingly in a dose-dependent manner （at 25 and 12.5 μM）. Conclusion We revealed that quercitin treatment led to the decrease of ROS and improvement of ATP， which triggered the protection of mitochondria from quercitin， thereby protecting them from OGD-induced neuronal injury and death.