The antineoplastic gefitinib has a low aqueous solubility, leading to poor absorption rates. To overcome this problem, microparticles (MP) were prepared using solution-enhanced dispersion by supercritical fluids (SEDS) with supercritical CO2 and the cosolvents dichloromethane and ethanol. The results showed that the use of SEDS resulted in the formation of smaller particles and rendered the usually heterogeneous crystals of the crude drug pure and uniform. Furthermore, the reduction in the MP size increased the dissolution rate of gefitinib, and in vitro cytotoxicity assays indicated that the MP inhibited the proliferation of A549 cells to a larger extent than did the crude drug. Given the beneficial properties of the MP, SEDS could potentially be used to micronize drugs for therapeutic applications.