〔Abstract〕 Objective To investigate novel antimicrobial agents targeting FtsZ. Methods Identification of potential molecules targeting FtsZ by structural-based virtual screening using Discovery Studio 2017 software in a variety of ways. Determination of antibacterial effect againstS.aureusof small molecule by broth dilution method. Molecular dynamics simulation was used to evaluate the binding stability of small molecule to FtsZ protein. Results Fiftymolecules with potential drug ability and excellent binding ability were obtained by virtual screening. All compounds exhibit certain antimicrobial effects on MSSA and MRSA. Among them, compound 5010-0572 showed best activity against MSSA and MRSA, with MIC value of 1 μg/ml. Molecular dynamics simulation illustrated that compound 5010-0572 with best antimicrobial effects bound to FtsZ better than compound C592-0444 with lowest antimicrobial effects. Conclusion The antimicrobial effects of small molecules targeting FtsZ is closely related to the binding stability with protein. Compound 5010-0572, which has notable antimicrobial activity, may become a leading compound for the development of new antimicrobial agent.