Abstract: In order to improve the application of acetylated starch in biomedicine and targeted drug delivery system, ordinary corn starch was selected as the material, acid hydrolysis in alcohol medium before the acetylation was introduced in the preparation of the acetylated acid-hydrolysis modified starch with high degree of substitution. The effects of acid-hydrolysis conditions on physicochemical properties of the modified starches were investigated by means of FT-IR, XRD, contact angle measurement, pasting curve and scanning electron microscope. Subsequently, anti-solvent precipitation was introduced in the preparation of the starch nanoparticles, and the size range was determined. Based on the results, under the condition of 70% ethanol (v/v), 12 mol/L hydrochloric acid and 65 ℃, the substitution degree of acetylated starch increased from 0.84 to 1.33, the hydrophobicity significantly (P<0.05) improved and the particle size was reduced. Starch nanoparticles with a particle size of about 200 nm could be obtained through anti-solvent precipitation.