An effective strategy to synthesize 2,4-diaminoquinoline compounds has been efficaciously developed via a TMSOTf/TfOH-promoted [4 + 2] annulation of ynamides with 2-aminoarylnitriles. Compared with the reported transition-metal catalysts, this metal-free promotion system presented a remarkable advancement, enabling the facile and regiospecific assembly of 2,4-diaminoquinoline frameworks with wide functional group compatibility and moderate to excellent yields.