It is generally assumed that a central metal is essential for the efficiency of phthalocyanines in photodynamic therapy (PDT) of cancer. Contrary to the set opinion, the results of the present study indicate that the metal-free sulfonated phthalocyanines (H₂PcS_n, where n is the number of sulfonate groups per molecule) possess a considerable photoactivity. The relative phototoxicities of H₂PcS_1.5, H₂PcS_2.4, H₂PcS_3.1 and H₂PcS_3.8 on HEp2 human epidermoid carcinoma cells were 3.3, 20, 3.3 and 1, respectively, thus demonstrating dependence of the activity on the sulfonation degree, known for metallo-PcS_n. A significant delay in tumor growth and a decrease in tumor regrowth rate were observed in mice after PDT with H₂PcS_2.4. The antitumor effect declined in the order H₂PcS_2.4 > H₂PcS_3.1 > H₂PcS_1.5 and vanished for H₂PcS_3.8. We demonstrate here that the high photodynamic activity of H₂PcS_2.4 can be explained by its physicochemical properties in living cells and tissues. Thus, H₂PcS_n (n is about 2) can be considered as a new alternative in PDT of light-accessible neoplasms and further clinic-oriented studies are warranted.