A domino three-component strategy with high efficiency for the synthesis of spiro[indoline-3,4-pyrazolo[3,4-b]pyridines] from easily available isatins, pyrazol-5-amines and -ketonitriles under microwave heating. During reaction process, HOAc plays dual roles as reaction media as well as a BrOnsted acid-promoter. Flexible structural modification, broad functional group compatibility and mild reaction conditions make this strategy a useful and attractive process of library generation for drug discovery.