5-fluorouracil-SiO(2)-poly(L-lactide) (5-Fu-SiO(2)-PLLA) microcapsules were prepared in a novel process of solution-enhanced dispersion by supercritical CO(2) (SEDS). The SiO(2) nanoparticles were loaded with 5-Fu by adsorption at the first place, then the 5-Fu-SiO(2) nanoparticles were coated with PLLA by a modified SEDS process. The resulted microcapsules were characterized by scanning electron microscope (SEM), laser diffraction particle size analyzer, Fourier transform infrared spectrometer (FTIR) and thermogravimeter-differential scanning calorimeter (TG-DSC). The drug load, encapsulation efficiency and drug release profiles were also determined. The resulted microcapsules exhibited a rather spherical shape, smooth surface, and a narrow particle size distribution with a mean particle size of 536 nm. The drug load and encapsulation efficiency of the samples were 0.18% and 80.53%, respectively, 25.05% of 5-Fu was released in the first half hour, then drug released in a sustained process, which was much slower than that of without coated by PLLA. The results indicated that the modified SEDS process could be used to produce drug-polymer microcapsules with a core-shell structure, high encapsulation efficiency and sustained drug release effect.