Cerebral?ischemia/reperfusion?(I/R) usually leads to the exacerbation of brain?injury. In the present research, the effect of BTB and CNC homology 1 (BACH1) on?cerebral?I/R?injury?was studied. Mice model of middle?cerebral?artery occlusion/reperfusion?(MCAO/R) and Neuro-2a (N2a) cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) were established to investigate the role of?BACH1. It was found that MCAO/R mice expressed much higher?BACH1?in the brain tissues accompanied with severe?cerebral?infarction, whereas?downregulation?of?BACH1?reduced the infarction in MCAO/R mice. TUNEL staining showed that the?downregulation?of?BACH1?inhibited apoptosis in brain tissues of MCAO/R mice. The expression of cleaved caspase-3 and cleaved PARP were also decreased by the?downregulation?of?BACH1. Reactive oxygen species (ROS) and 3-nitrotyrosine (3-NT) staining showed that the?downregulation?of?BACH1?reduced the levels of ROS and 3-NT. Moreover, less malondialdehyde (MDA) and more superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were detected in MCAO/R mice pretreated with?BACH1?shRNA, indicating that the?downregulation?of?BACH1?reduced the oxidative stress. Similar conclusions were obtained from the further studies on N2a cells of OGD/R. We found that the?downregulation?of?BACH1?reduced cell damage, oxidative stress and apoptosis in N2a cells. It was also demonstrated that the?downregulation?of?BACH1?functioned through?HO-1?and?NQO1, which played important roles in protecting?against?cerebral?I/R?injury. Thus,?BACH1?might be a potential therapeutic target for preventing?cerebral?I/R?injury.