A drug vaccarin loaded polymer poly (vinyl alcohol) (PVA)-stilbazole quaternized (SbQ)/Zein was prepared in this study, using co-electrospun method. Then the morphologies and structures of PVA-SbQ/Zein composite nanofibers were observed by scanning electron microscope (SEM) and Fourier transform infrared spectrum (FTIR), respectively. Finally, biocompatibility of PVA-SbQ/Zein nanofibers with drug and without drug was evaluated. Results showed that vaccarin-loaded PVA-SbQ/Zein nanofibers had smooth surface and showed non-toxic to L929 cells. Drug vaccarin could promote cells attachment on nanofibers. The wound healing performance was examined in vivo by rat skin models and histological observations, and PVA-SbQ/Zein/vaccarin nanofibers showed better wound healing performance than petrolatum gauze group.