〔Abstract〕 Objective To explore the effect of sevoflurane post-conditioning on oxygen-glucose deprivation/reoxygenation(OGD/R) damage of primary hippocampal neurons, oxidative stress and autophagy. Methods Hippocampal neurons were cultured in uterine endometrial rats for(18±0.5) days. After 7 days, the cultured hippocampal neurons were randomly divided into three groups: normal control group(CON group), oxygen-glucose deprivation/reoxygenation(OGD/R) group and sevoflurane post-conditioning group(OGD/R+SEVO group). Primary hippocampal neurons in the CON group were cultured normally; OGD/R group was treated with oxygen-glucose deprivation for 1.5 hours and reoxygenation for 24 hours to establish oxygen and glucose deprivation/reoxygenation injury model; OGD/R+SEVO group was treated with sevoflurane for 1 hour and then reoxygenated for 23 hours. After treatments, the activity of each group of LDH was detected by colorimetric method, TUNEL staining method detected the changes of hippocampal nerve cells in each group, immunofluorescence method detected mitochondrial ROS and the expression of autophagy proteins LC3 B,and Western blot analysis detected the expression of PINK1 and Parkin. Results Compared with CON group, the release of lactate dehydrogenase increased(P<0.01); neuronal apoptosis increased; mitochondrial ROS and the expression of autophagy marker proteins LC3 B increased(P<0.01), PINK1 and Parkin also increased in OGD/R group(P<0.001,P<0.05). Compared with OGD/R group, the release of lactate dehydrogenase was reduced(P<0.05), the apoptosis was inhibited, mitochondrial ROS and the expression of autophagy marker proteins LC3 B were reduced(P<0.05), PINK1 and Parkin protein were reduced(P<0.01,P<0.05) in OGD/R+SEVO group. Conclusion Sevoflurane post-conditioning can protect primary hippocampal neurons by reducing OGD/R-induced excessive autophagy, reducing oxidative stress, and reducing apoptosis, and its mechanism of reducing autophagy may be related to the PINK1/Parkin pathway.