A series of substituted ortho-carboranylphenoxyacetanilides were synthesized and evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter assay in HeLa cells expressing the HRE-dependent firefly luciferase reporter construct (HRE-Luc) and constitutively expressing CMV-driven Renilla luciferase reporter, and their ability to inhibit cell growth (GI 50 ) using the MTT assay. Among the compounds synthesized, 1g and 1l showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity (IC 50 : 1.9±0.4 and 1.4±0.2μM, respectively). Both compounds suppressed HIF-1α accumulation in a concentration-dependent manner. The porcine heart malate dehydrogenase (MDH) refolding assay revealed that compound 1l inhibited human Hsp60 chaperone activity (IC 50 : 6.80±0.25μM) and this inhibition activity was higher than that of ETB (IC 50 : 10.9±0.63μM).