5-Fluorouracil (5-Fu) loaded poly(glycolideco-lactide-co-caprolactone) (PGLC) nanoparticles were prepared by modified spontaneous emulsification solvent diffusion method (modified-SESD method) and characterized by dynamic light scattering, scanning electron microscopy and H NMR determination. It was found that the obtained nanoparticles showed near spherical shape and was controllable with the radius range of 30-100 nm. Compared with the nanoparticles prepared by polylactide and poly (lactide-co-glycolide) (PLGA) under the similar preparation condition, yield of PGLC nanoparticles was the highest, which reached to about 100%. On the other hand, drug entrapment efficiency of PGLC nanoparticles was also higher than that of PLGA and PLLA nanoparticles. 5-Fu release behavior of PGLC nanoparticles in vitro showed that 5-Fu release of PGLC nanoparticles showed a near zero-order release profile, and 5-Fu release rate of PGLC nanoparticles was faster than that of PLLA and PLGA nanoparticles. According to degradation behavior of PGLC nanoparticles, it could be proposed that the kinetic of degradation controlled release played an important role in the release process of PGLC nanoparticles. It revealed that the PGLC nanoparticles could be a promising drug carrier.