Abstract: The present invention relates to a HIF-l? activator containing clioquinol and its derivatives as an active ingredient. Clioquinol and its derivatives of the invention inhibit HIF-1?(hypoxia-inducible factor-l?) ubiquitination in normoxic cells and thus accumulate HIF-l?. In the meantime, CQ inhibits FIH-I activity and thereby induces transcription activity of the accumulated HIF-l?, resulting in the induction of expressions of HIF-l? target genes VEGF (vascular endothelial growth factor) and EPO (erythropoietin). Therefore, clioquinol and its derivatives can be effectively used as a therapeutic agent for ischemic disease.