The current study aimed to elucidate the effects of Sevoflurane on neuronal autophagy and ischemic brain injury by regulating miR-7a/ATG7 axis. The rat model of middle cerebral artery occlusion (MCAO) was established by thread embolization. The expression pattern of microRNA-7a (miR-7a) and autophagy-related gene 7 (ATG7) was subsequently determined in Sevoflurane-treated MCAO rats with their relation and effects on neuronal autophagy and ischemic brain injury further analyzed. Bioinformatics analysis confirmed that miR-7a could target to inhibit ATG7 in ischemic brain injury samples. Sevoflurane could alleviate ischemic brain injury in rats by reducing the level of neuronal autophagy-related factors. The expression of miR-7a was up-regulated and ATG7 was down-regulated in the brain tissues of MCAO rats after Sevoflurane treatment. ATG7 was found to induce neuronal autophagy during autophagy in the brain tissues of MCAO rats. In summary, Sevoflurane exerts protective effects on ischemic brain injury via inhibiting autophagy of neurons and microglia through the miR-7a-mediated downregulation of ATG7. •Sevoflurane alleviated ischemic brain injury in rats by reducing autophagy.•Sevoflurane upregulated miR-7a to inhibit ischemic brain injury.•miR-7a negatively regulates the expression of ATG7.•ATG7 reversed the protective effect of Sevoflurane on ischemic brain injury.•The study highlights a new preventive option for ischemic brain injury.