Bioassay-directed fractionation employing a multidrug-resistant (MDR) strain of Staphylococcus aureus. resulted in the isolation of an antibacterial prenyl substituted xanthone derivative (1) named hyperixanthone A from the root of Hypericum sampsonii. Hance (Hyperiaceae). Compound 1 showed promising inhibitory activity against the norfloxacin-resistant S. aureus. strain SA-1199B at a minimum inhibitory concentration (MIC) of 2 μ g/mL (4.3 μ M), wheres the positive standard antibacterial drug norfloxacin showed an MIC of 32 μ g/mL (100 μ M). This strain overexpresses the NorA multidrug efflux transporter, the major characterized drug pump in Staphylococcus aureus.. The activity of this compound against an effluxing strain of S. aureus. is reported here for the first time. Compound 1, together with 1,7-dihydroxyxanthone (2) and 2-hydroxyxanthone (3), were obtained by silica gel column chromatography, and their structures were determined by means of extensive NMR and MS spectra.