The first HFIP-promoted catalyst-free cascade reactions for the synthesis of biologically relevant 3,3-di (indolyl)indolin-2-ones (27 examples, up to 98％ yield) from readily available indoles and isatin derivatives are described. This protocol shows well tolerance of different functional groups and features mild reaction conditions such as short reaction time (～ 1 h), no usage of catalyst, easy operation and product isolation. Of particular interest is the formation of two C--C bonds and one all-carbon quaternary center. This protocol could serve as an alternative strategy to synthesize biologically important 3,3-di (indolyl)indolin-2-ones for biological testing.