The ibuprofen (IBU) was selected as a model of the poor-water drugs, and the IBU-loaded chitosan/β-cyclodextrin/trisodium citrate nanoparticles were prepared via the ionic cross-linking method. The drug-loading capacity, particle size, zeta potential and surface morphology of the obtained nanoparticles were characterized. The results showed that the IBU had been successfully loaded into the nanoparticles, and showed good drug-loading capacity. The prepared nanoparticles were spherical morphology with an average size of 293.7 nm and a Zeta potential of +30.72 mV. The in vitro release studies showed that the controlled release of IBU from the nanoparticles was followed.