In this study, sophoraflavanone G obtained from Sophora flavescens was evaluated against 10 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), either alone or in combination with ampicillin or oxacillin, via checkerboard assay. At the end point of an optically clear well, the minimum inhibitory concentrations (MICs) ranged from 0.5 to 8 microg/ml for sophoraflavanone G, from 64 to 1024 microg/ml for ampicillin, and from 256 to 1024 microg/ml for oxacillin. The combination of sophoraflavanone G and ampicillin or oxacillin yielded a fractional inhibitory concentration index ranging from 0.188 to 0.375, thereby indicating a principally synergistic effect. The synergistic interaction was verified by time-kill studies using sophoraflavanone G and/or antibiotics. Thirty minutes of treatment with sophoraflavanone G with ampicillin or oxacillin resulted in an increase in the rate of killing in units of CFU/ml to a greater degree than was observed with Sophoraflavanone G alone. These findings indicated that the application of the tested sophoraflavanone G alone or in combination with antibiotics might prove useful in the control and treatment of MRSA infections.