Mathematical modeling for 5-fluorouracil (5-FU) nanoparticle synthesis via gas antisolvent (GAS) process was investigated. 5-FU was precipitated from a dimethyl sulfoxide (DMSO) solution using CO2 as antisolvent. The particle size was controlled by nucleation and growth rates, therefore, the kinetic modeling study is essential. Thermodynamic modeling was applied to determine optimal operating conditions for experimental 5-FU synthesis. Kinetic parameters were evaluated by fitting the particle size distribution predicted by the model to experimental data. The experimental and modeling results indicated that the particle size decreased with increasing the antisolvent addition rate.