In this study we aimed to develop a new targeted nanoparticulate system to obtain site specific delivery of ibuprofen and to determine its antitumor efficiency. The potential effect of ibuprofen as an antitumor agent was investigated on breast cancer cells based on a targeted delivery system. Ibuprofen was encapsulated to poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA nanoparticles were fabricated by nanoprecipitation method and optimized in terms of certain parameters. Then, 520C9 monoclonal antibody (mAb) was chemically conjugated to carboxylic acid end group of PLGA nanoparticles (NPs) that specifically targeted human breast adenocarcinoma cell line (MCF-7), NP-mAb combined Ibuprofen encapsulated formulations were evaluated on characterization of particle size, encapsulation efficiency, drug loading capacity, and antitumor activity. The results demonstrated that optimized Ibuprofen loaded PLGA nanoparticles prepared by nanoprecipitation technique had an ideal particle size and polydispersity index. The encapsulation efficiency of optimized nanoparticles was relatively high, 92.9 +/- 9.0 %. Also, this system had significantly reduced the cell viability on MCF-7 cell line when compared with free ibuprofen solution at the same concentration. Above all, antibody-conjugated nanoparticles showed lower cell viability (12%) than the non-targeted system. Results indicated that ibuprofen-loaded nanoparticles had significant antitumor activity on MCF-7 cells even at relatively low concentrations. mAb conjugated drug-loaded nanoparticles were successfully fabricated and this system might be a promising approach for delivery of ibuprofen in treatment of breast cancer.