Background and Objective: Methicillin-resistant Staphylococcus aureus is an important pathogen in medicine. Different studies have shown that some plant-derived materials loaded in a drug delivery system such as nanoliposomes could inhibit growth of resistant bacteria. Silymarin is an effective compound from medicinal plant Silybum mariunum L. The aim of this study was to prepare silymarin-loaded nanoliposomes and evaluate their efficacy against resistant staphylococcus aureus in vitro. Materials and Methods: Silymarin-loaded nanoliposomes were prepared by reverse phase evaporation method. Then, the minimum inhibitory concentration (MIC) of silymarin-loaded nanoliposomes for resistant strain of Staphylococcus aureus was determined by broth dilution method. Ultimately, the killing rate of Staphylococcus aureus at MIC concentration of silymarin in free and nanoliposomal form was analyzed. Results: In this study, the encapsulation efficacy for silymarin-loaded nanoliposomes was 83%±0.17. The MICs of free and nanoliposomal form of silymarin against resistant strain of Staphylococcus aureus were 500 and 125 mg/l, respectively. The killing rate of silymarin-loaded nanoliposomes was higher than that of free silymarin at identical times. Conclusion: Our data suggest that the prepared silymarin-loaded nanoliposomes due to high effectiveness would be a good choice for the treatment of Staphylococcus aureus infections.