The anodized titanium nanotubes (TiO2-NTs) are considered to be a potential material in clinical therapy. To enhance the antibacterial property of TiO2-NTs, cefuroxime is introduced into TiO2-NTs, and then, different chitosan layers are coated to control the release of cefuroxime. SEM and FTIR are adapted for the characterization of prepared TiO2-NTs. The effects of chitosan coating thickness on release of cefuroxime are also investigated, followed with the antibacterial property evaluation. The results show TiO2-NTs are fabricated by anodization method and cefuroxime is also successfully loaded into the nanotubes. The thickness of chitosan coating is an important factor to the release rate of cefuroxime. Antimicrobial detection and morphology observation of S. aureus show a sustained 7-day drug release and strong negative effect on bacteria. The approach in this study provides a broadly applicable method to fabricate titanium-based orthopedic implants with enhanced antibacterial properties.