Methicillin-resistant Staphylococcus aureus (MRSA) is emerging as a serious pathogenic bacterium in the clinical setting, and antibiotic resistance is spreading faster than the introduction of new agents to kill such bacteria. In our study, Fusarium sp. 152, a marine fungus obtained from the South China Sea, was fermented to screen new anti-MRSA compounds including equisetin (EQ) with a MIC value of 1 mu g/mL. Then, EQ was loaded into nanoparticle- based polyvinylpyrrolidone (PVP) electrospinning to facilitate its practical use. After electrospinning, the EQ nanofibers (EQ/NPs nanofiber) were 374.9 nm in diameter, and they showed a good flexibility and foldability. Additionally, the EQ/NPs nanofibers showed a better antibacterial effect both in vitro and in vivo than cefoxitin. Simultaneously, the infectious wounds treated with EQ/NPs nanofiber healed better and faster than those treated with EQ and cefoxitin. These findings strongly demonstrate that PVP-based electrospinning dressings are a candidate delivery carrier for the new anti-MRSA compound EQ for topical therapy.