Amino-substituted tetraphenylporphyrin derivatives have been designed as pH-activatable photosensitizers for photodynamic cancer therapy. The photophysical processes of the monoamino-substituted derivative N1 and nonsubstituted derivative NO have been studied. The quantum yields of the fluorescence and photosensitization of singlet oxygen by N1 were very low in the neutral condition (OFF state), but these quantum yields were recovered by adding acid (ON state). These changes were not observed for NO; therefore, N1 is expected to be applicable as a pH-activatable photosensitizer. The ON/OFF switching mechanism of N1 has also been clarified. To optimize the pH response, tri- and tetraamino-substituted derivatives (N3 and N4) have also been explored. The pH response intensified as the number of amino groups increased. Furthermore, the ON/OFF switching ratio of N3 was 100, which is quite high.