Recrystallzation and micronization of 10-hydroxycamptothecin (HCPT) was investigated in a supercritical antisolvent (SAS) process using the mixture of dichloromethane and ethanol as the solvent, with supercritical carbon dioxide (sc-CO2) as the antisolvent. Five factors-i.e., the volume ratio of the mixed solvent, the concentration of HCPT in the solution, the flow rate of HCPT solution, the precipitation pressure, and the temperature-were optimized using a selected OA(16) (4(5)) orthogonal array design. The unprocessed and processed HCPT particles were characterized using laser diffraction particle size analysis, Fourier transform infrared (FT-IR) spectroscopy, headspace gas chromatography, scanning electron microscopy (SEM), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The results indicated that the micronized HCPT exhibited a much smaller particle size under the optimal conditions, and the mass median diameter of the micronized HCPT was found to be 223 +/- 19 nm. SEM indicated a change in crystal habit for SAS-processed particles, and the results of powder XRD showed that different polymorphs were found after the SAS processing. Polymorph conversation was further demonstrated by DSC and TGA, and the results indicated that the SAS process modified the form of HCPT from monohydrate to anhydrous.