〔Abstract〕 Objective To explore the effects of different concentrations of sevoflurane on the apoptosis, self-renewal and neural differentiation of human embryonic stem cells(hESCs). Methods hESCs were treated with 2.1%(low-dose) or 4.1%(high-dose) sevoflurane for 6 hours. Alkaline phosphatase staining, quantitative real-time PCR, Western blot and immunofluorescence were used to detect the levels of markers of apoptosis, self-renewal and neural cells. Meanwhile, the total and phosphorylated proteins of SMAD and ERK were also examined. Results Compared with the no treatment control cells, there was no significant change in the apoptosis, undifferentiated state and neural differentiation of hESCs in the low-dose group cells. However, the apoptosis of hESCs was induced by the treatment of high-dose sevoflurane. Consistently, the protein level of CASPASE3(P<0.05), an apoptotic marker, increased. At the same time, many hESC colonies partially differentiated, characterized by the downregulation of self-renewal markersOCT4,SOX2,NANOGandPRDM14 and the upregulation of differentiation associated genesGATA4 andGATA6(P<0.01). Moreover, the high-dose sevoflurane inhibited the efficiency of neural differentiation of hESCs, shown by the lower expression levels of neural cell markersTUJ1,ASCL1 andMAP2(P<0.05) when compared with control and low-dose group cells. In addition, the treatment of high-dose sevoflurane reduced the phosphorylation level of ERK in hESCs(P<0.05), suggesting that the effect of high-dose sevoflurane may be related to the ERK signaling. Conclusion High concentration of sevoflurane has a certain inhibitory effect on the self-renewal and neural differentiation of hESCs. The downstream mechanism is partially associated with the decreased activity of ERK signal. Our study will provide useful clues for the safe application of sevoflurane in the future.