Nanofiber mats have been widely applied in various biomedical fields such as drug delivery, tissue repair and wound dressing. In this study, the curcumin-loaded mesoporous silica incorporated nanofiber mats were prepared using blend electrospinning of curcumin-loaded mesoporous silica nanoparticles (CCM-MSNs) and polyvinyl pyrrolidone (PVP) for hemostasis. The prepared mats were then evaluated to determine their structure, biocompatibility and antibacterial activity, especially focusing on the hemostatic effect using an in vivo liver injury model. The results showed that CCM-MSN loading ratios less than 8 wt% could be homogeneously dispersed in the PVP electrospun nanofibers. The in vitro studies demonstrated that the hybrid nanofiber mats had no obvious toxic effect on the growth of L929 cells. The hybrid nanofiber mats also exhibited enhanced in vitro antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). The antibacterial effect of the hybrid nanofiber mats was further confirmed by in vivo experiments. Moreover, the in vivo hemostasis studies revealed that the hybrid nanofiber mats could rapidly transform into hydrogel when they contact with blood, and then activate the clotting system to stop the wound bleeding. Therefore, the CCM-MSN incorporated PVP nanofiber mats provide a practical possibility for nanofiber-based hemostatic materials with good biocompatibility and high antibacterial activity.