In order to achieve the purpose of targeting treatment of osteosarcoma, we developed novel paclitaxel (PTX) nanoparticles (Nps) coated with polydopamine (PDA) and grafted by alendronate (ALN) as ligand. Dopamine can be easily polymerized on various surfaces to form a thin PDA film in alkaline environment, which provided a versatile platform to perform secondary reactions for compounds without functional groups. The targeting Nps had a mean particle size of 290.6 ± 2.2 nm and a zeta potential of -13.4 ± 2.7. It was stable in phosphate buffer saline (PBS, pH 7.4), 5% glucose, plasma and displayed sustained drug release behavior. In vitro assay demonstrated the targeting Nps had stronger cytotoxicity against K7M2 wt osteosarcoma cells than the non-targeting Nps. Furthermore, in vivo distribution study indicated they could accumulate much more in tumor than non-targeting Nps. This is consistent with the in vivo antitumor study, targeting Nps achieved a better therapeutic effect than Taxol (8 mg kg-1, i.v.) (71.85% versus 66.53%) and prominently decreased the side effects of PTX. In general, the PTX-PDA-ALN-Nps may offer a feasible and effective strategy for osteosarcoma targeted therapy.