This present study was aimed to investigate the molecular mechanisms involved in sevoflurane protection of hepatic ischemia-reperfusion (I/R) injury. Firstly, we investigated the protective effects of sevoflurane against hepatic I/R injury. Biochemical analysis results showed that sevoflurane preconditioning significantly protected against hepatic I/R injury by reducing liver enzymes and improving antioxidant defense markers. We also found that sevoflurane attenuates I/R-induced hepatic cell death, by TUNEL staining, DNA fragmentation ELISA and PARP activity determination. Next, In order to find the molecular mechanism of sevoflurane preconditioning in hepatic I/R injury, we poured our attention to microRNAs regulation. We focused on miR-200c, one of microRNAs which screened from the gene expression omnibus (GEO). Furthermore, a hydrogen peroxide (H₂O₂)-induced oxidative stress apoptosis model was also established to mimic hepatic I/R injury, the effects of MiR-200c was investigated. We observed that MiR-200c inhibition decreased the H₂O₂-induced apoptosis of hepatic AML-12 cells. And also, ZEB1 is found as a target gene of miR-200c and is involved in H₂O₂-induced apoptosis. On the other hand, the in vivo model was established to examine whether sevoflurane protect against hepatic IR injury by downregulating MiR-200c. Together with the biochemical tests and apoptosis detection, results showed that over-expression of miR-200c significantly inhibited the protect effect of sevoflurane in Hepatic IR injury. Summarizing, sevoflurane preconditioning seems to ameliorate hepatic I/R injury in mice, mediated by mechanisms that include microRNA 200c down regulation. However, further more studies need to be carried out to verify this point.