Objective To investigate the effects of isoflurane and sevoflurane on migration and expression of cell division cycle 42 (Cdc42), Fascin of human adenocarcinoma cell line A549. Methods A549 cells were inoculated in culture plate. After being cultured for 24 h the cells were randomly divided into 3 groups: group control (C), group 2.3 % isoflurane (Iso), and group 3.4% sevoflurane (Sev). Each group contained 6 wells. A549 cells of group Iso and Sev were exposed to 2.3% isoflurane or 3.4%sevoflurane for 2, 4, and 6 h respectively. Cells of group C were exposed to 95%O2-5%CO2 mixture air, and were then cultured for additional 24 h. The migration of A549 cells were assessed by Transwell cell culture chamber. The expression Cdc42 and Fascin in A549 cells were detected by Wester blotting at 24 h after isoflurane and sevoflurane treatment for 4 h. Results Compared with group C and group Sev，the number of migration cells in group Sev was significantly decreased (P <0.05). The expression of Cdc42 in group Sev was significantly down-regulated as compared with group C and group Iso [(75±16)%，(79±13) % vs (31±7) %] (P <0.05); The expression of Fascin in group Sev was significantly down-regulated as compared with group C and group Iso [(71±13)%，(77±18)% vs (40±8)%]（P <0.05）. Conclusion Sevoflurane can inhibit the migration of A549 cells through down-regulating the expression of Cdc42 and Fascin. Isoflurane can not inhibit the migration of A549 cells.