Phytochemical investigation of the twigs of Zanthoxylum armatum DC. led to the extraction and isolation of twenty-one compounds, including nine phenolic acids (1–9), a steroid (10) and eleven lignans (11–21). The structures of these compounds were elucidated by NMR spectroscopic analysis, and comparison with the reported data. Compounds 1–7, 15, 17, 18, and 21 were first obtained from Z. armatum. Among them, compounds 1–3, 7 and 21 were also first isolated from the family Rutaceae. The anti-hypoxia evaluation of the isolated compounds was carried out by using PC12 cells, and the results showed that compounds 2, 3, 5, 7, 8, 12 and 14 had potential anti-hypoxia activity. In addition, the chemotaxonomic significance of the isolates was discussed in detail, which might provide important chemical taxonomic evidence.