【Abstract】 Objective To investigate the regulatory effect and mechanism of miR-155-5p mimic targeting hypoxia inducible factor 1α (HIF-1α) on the growth and motility of nonsmall cell lung cancer A549 cells. Methods The untransfected A549 cells growing in logarithmic phase ells were set as control group. miR155 mimic and HIF-1α were transfected into A549 cells respectively, which were divided into Mir155 mimic group and HIF1α group. Then they were co transfected into A549 cells and set up as mimic+HIF1α group. The targeting relationship between Mir 375 and SLC7A11 was detected by luciferase reporter gene. The mRNA expression levels of Mir-155-5p and HIF1α were detected by RT PCR. The cell proliferation was detected by Edu staining. The cell migration was detected by scratch test. The cell invasion was detected by Transwell chamber test. The protein expression was detected by Western blot. Results HIF-1α is the target gene of Mir-155-5p mimic. Compared with control group, HIF-1α mRNA level, HIF-1α and Ki67 protein expression, proliferative cell number, invasive cell number and scratch healing rate were all decreased in miR155 group (P＜0.05), while HIF-1 α mRNA level, HIF-1α and Ki67 protein expression, proliferative cell number, invasive cell number and scratch healing rate were all increased in HIF1α group (P＜0.05). Compared with HIF-1α group, HIF-1α mRNA level, HIF1α and Ki67 protein expression, proliferative cell number, invasive cell number and scratch healing rate were all decreased in mic+HIF-1α group (P＜0.05). Compared with the control group, the expression of N cadherin, VEGF, VEGFR2, p38 protein in miR155mic group decreased, E cadherin protein increased (P＜0.05), N cadherin, VEGF, VEGFR2, p38 protein in HIF-1 α group increased, E cadherin protein decreased (P＜0.05). Compared with HIF1α group, the expression of N cadherin, VEGF, VEGFR2 and p38 protein in mic+HIF-1α group decreased, while the expression of E cadherin protein increased (P＜005). Conclusion miR-155-5p can inhibit the proliferation, invasion and migration of nonsmall cell lung cancer A549 cells by targeting the expression of HIF-1α. Its mechanism may be related to the inhibition of epithelial stromal transformation and VEGF/p38 pathway.