Objective(s): Scutellarin, a flavonoid extracted from the medicinal herb Erigeron breviscapus Hand-Mazz, protects neurons from damage and inhibits glial activation. Here we examined whether scutellarin may also protect neurons from hypoxia-induced damage. Materials and Methods: Mice were exposed to hypoxia for 7 days and then administered scutellarin (50 mg/kg/d) or vehicle for 30 days Cognitive impairment in the two groups was assessed using the Morris water maze test, cell proliferation in the hippocampus was compared using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry, and hippocampal levels of nestin and neuronal class III β-tubulin (Tuj-1) were measured using Western blotting. These results were validated in vitro by treating cultured neural stem cells (NSCs) with scutellarin (30 μM). Results: Treating mice with scutellarin shortened escape times and increased the number of platform crossings, it increased the number of BrdU-positive proliferating cells in the hippocampus, and it up-regulated expression of nestin and Tuj-1. Treating NSC cultures with scutellarin increased the number of proliferating cells and the proportion of cells differentiating into neurons instead of astrocytes. The increase in NSC proliferation was associated with phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, while neuronal differentiation was associated with altered expression of differentiation-related genes. Conclusion: Scutellarin may alleviate cognitive impairment in a mouse model of hypoxia by promo-ting proliferation and neuronal differentiation of NSCs.