【Abstract】 Objective To investigate the effect of microRNA-424 (miR-424) on neuronal apoptosis after cerebral ischemia in mice. Methods The lentiviral mediated overexpression of miR-424 (109U/ml, 8ul) was injected into the lateral ventricle in mice for 7d, then the middle artery occlusion (MCAO) model was established, and the mice were divided into 4 groups: sham group, sham miR-424 group, MCAO model group and MCAO miR-424 group (N=6). At 8h after MCAO, the ischemic brain tissue was removed and paraffin sections were used to perform TUNEL staining to observe neuronal apoptosis, and the protein levels of transcription factor PU.1, hypoxia inducible factor-1α (HIF-1α), apoptosis-related proteins p53 were detected by western blot. Results The TUNEL immunofluorescence indicates that miR-424 can reduce neuronal apoptosis at 8h after cerebral ischemia in mice, and western blot showed that, before ischemia or at 8h after ischemia, the effect of miR-424 on three proteins expression is the same for normal or MCAO model brain tissue, increasing the levels of PU.1, HIF-1α and apoptotic protein p53. Conclusion miR-424 can reduce neuronal apoptosis after cerebral ischemia partly through increasing expression of transcription factor PU.1 and HIF-1α, as well as apoptosis-related proteins p53 in the brain tissue of mice.