Tetracycline hydrochloride loaded poly (vinyl alcohol)/chitosan/ZrO2 (Tet-PVA/CS/ZrO2) hybrid nanofibers were fabricated via electrospinning technique. The representative weight ratio of PVA/CS at 3 : 1 was chosen to fabricate drug carrier PVA/CS/ZrO2 nanofibers. The drug carrier showed a decrease in average diameter with the increase of ZrO2 content at given conditions, and the nanofibers were uneven and interspersed with spindle-shape beads with ZrO2 content at 60 wt % and above. The networks linked by hydrogen and Zr-O-C bonds among PVA, CS, and ZrO2 units resulted in the improving of thermal stability and decreasing of crystallinity of the polymeric matrix. Moreover, the incorporation of ZrO2 endowed the fibers with ultraviolet shielding effect ranged from 200 to 400 nm. The Tet loading dosage had no obvious effect on the morphology and size of the medicated nanofibers at Tet content below 8 wt %, but interspersed with spindle-shaped beads when Tet content increased to 10 wt %. The Tet-PVA/CS/ZrO2) nanofibers showed well controlled release and better antimicrobial activity against Staphylococcus aureus, and the Tet release from the medicated nanofibers could be described by Fickian diffusion model for M-t /M< 0.6. These medicated nanofibers may have potential as a suitable material in drug delivery and wound dressing. (c) 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42506.