||Multidrug resistance (MDR) resists further chemotherapy and causing cancer recurrence. The application of low pH lysosomes to stimulate the self-assembly effect of different materials have been studied. As disruption of lysosome integrity initiate cell death via lysosome and involved in various aspects of cell death, lysosome targeting cancer cell therapy is emerging as attractive strategy. Therefore, we designed molecules which can form supramolecular self-assembly in acidic condition of lysosome with different self-assembly ability by adjusting the pKa of each molecule. At acidic pH, molecules with higher self-assembly ability exhibit lower CAC and larger assembly size, which are efficient at inhibiting cancer cells through lysosomal-mediated cell death. This work provides insight into designing method for the specific organelle-targeted construction of supramolecular self-assembly for biomedical application and also suggests effective therapeutic strategy to inhibit MDR cancer cell.