Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was successfully synthesized from the reaction of hydroxypropyl methylcellulose with succinic anhydride and acetic anhydride in an acetone/pyridine system. Products with different contents of succinyl groups and acetyl groups were prepared by varying the reaction conditions. In the acetone/pyridine system, equipment corrosion does not occur, the product is easy to wash, and the solvent can be recycled. By varying the concentration of the esterifying agents, products with different ratios of acidic groups can be obtained. Under the optimum conditions, the obtained products had an average molecular weight between 5.39×10⁴ and 5.41×10⁴, a number average molecular weight from 4.97×10⁴ to 5.13×10⁴, and a polydispersity index from 1.05 to 1.08. The products dissolved well in acetone and methanol, and formed films on a mold. The films had good pH-sensitivity, tensile strength, and thermal stability. The formed films could dissolve in solutions with a pH value ranging from 5.4 to 6.4, and are therefore suitable for use as an enteric coating for pharmaceutical dosage forms.