Methicillin-resistant Staphylococcus aureus (MRSA) is a substantial contributor to morbidity and mortality. In search of a natural products capable of inhibiting this multidrug resistant bacteria, we have investigated the antimicrobial activity of brazilein (BRZ) isolated from Caesalpinia sappan L. (Leguminosae) against 8 different strains of Staphylococcus aureus (S. aureus). New antimicrobial activity was found using the minimum inhibitory concentrations (MICs), broth dilution as well as checkerboard method. Against the 8 strains, the minimum inhibitory concentrations of BRZ were in the range of 62.5-500μg/mL. From those results we performed the checkerboard test to determine the synergism of BRZ in combination with Hygromycin-b (HgB) against 4 strains. The combined activity of BRZ and HgB against 4 strains resulted in a fractional inhibitory concentrations index (FICI) ranging from 0.18-0.5. The effect of BRZ with HgB was found to be synergistic. We found that BRZ reduced the MICs of HgB. BRZ and HgB could lead to the development of new combination antibiotics against MRSA infection.