Spermine is an important biomarker for cancer diagnosis and treatment since it is dysregulated and overex-pressed in tumors. Herein, a supramolecular reporter pair PPDD@SC4AD is exploited by complexing amphiphilic sulfonatocalix[4]arene (SC4AD) with pyrido[1,2-a]pyrido[1 ',2 ':3,4]imidazo-[2,1-c]-6,7-dihydropyrazinium dibromide (PPDD). The reporter pair can detect spermine in biological systems. By detecting and depleting spermine, it realizes spermine imaging and induces apoptosis of tumor cells. SC4AD exhibits a high binding affinity and a strong complexation-induced fluorescence quenching effect. When complexing with spermine overexpressed in tumor cells, SC4AD can significantly release the fluorescence of PPDD. Moreover, spermine is efficiently encapsulated by calixarene to deplete spermine and induce apoptosis of tumor cells. The amphiphi-licity of SC4AD can drive the self-assembly of PPDD@SC4AD to guarantee an efficient enhanced permeability and retention effect in vivo. PPDD@SC4AD may inspire the development of new integrated approaches of diagnosis and treatment.