Abstract: OBJECTIVE To design, synthesis and biological evaluation of a series of 3-aryl-5-pyrazol-1,2,4-oxadiazole compounds as HIF-1 inhibitor.METHODS Through systematic modification on the linker and the substituents of phenyl ring, a series of novel target compounds were designed and evaluated HIF-1 inhibitory activity based on 3-aryl-5-para-Cl-benzyl- pyrazole-1,2,4-oxadiazole derivative 8.RESULTS Eighteen compounds exhibited moderate to good HIF-1 inhibitory activity and compound 11m was the most potent HIF-1 inhibitor with IC₅₀ value of 0.35 μmol·L^–1.Further biological evaluation of 11m revealed that it could inhibit HIF-1α protein expression and significantly prevented SKOV3 cells hypoxia-driven migration.CONCLUSION The SAR study of 3-aryl-5-pyrazol-1,2,4-oxadiazole derivatives as HIF-1 inhibitor pave the way for the further development of HIF-1 inhibitor.