The objective of this study was to apply the specific acid-catalysed hydrolysis of ethyl acetate to completing solvent extraction during an emulsion-based microencapsulation process. The dispersed phase consisting of poly-D,L-lactide-co-glycolide and ethyl acetate was emulsified in an acid catalyst containing aqueous phase. Catalytic hydrolysis of ethyl acetate led to its continual leaching from the dispersed phase of the emulsion, thereby triggering microsphere hardening with high efficiency. Ketoprofen was successfully encapsulated into microspheres via this technique, and liquid chromatography-mass spectrometry showed that its structural integrity was preserved during microencapsulation. Compared to typical solvent extraction approaches, the acid-catalysis technique helped minimize the consumption of a quench liquid. Also, the resultant microspheres displayed excellent dispersibility and decreased propensity for aggregation. Furthermore, the new method provided better drug encapsulation efficiency and lower levels of residual ethyl acetate in microspheres. In conclusion, the acid-catalysis approach had great potential for the preparation of versatile microspheres and nanoparticles.