Reactive oxygen species (ROS) formed by light activated photosensitizers (PSs) are the hallmark of photodynamic therapy (PDT). It is generally accepted that commonly used PSs generate singlet oxygen ((1)O2) as the cell-toxic species via type II photosensitization. We explored here the consequences of chemical modification and the influence of the net charge of a cationic tetrahydroporphyrin derivative (THPTS) relative to the basic molecular structure on the red-shift of absorption, solubility, mechanistic features, and photochemical as well as cell-toxic activity. In order to shed light into the interplay between chemical modification driven intra- and intermolecular photochemistry, intermolecular interaction, and function, a number of different spectroscopic techniques were employed and our experimental studies were accompanied by quantum chemical calculations. Here we show that for THPTS neither (1)O2 nor other toxic ROS (superoxide and hydroxyl radicals) are produced directly in significant quantities in aqueous solution (although the formation of singlet oxygen is energetically feasible and as such observed in acetonitrile). Nevertheless, the chemically modified tetrapyrrole photosensitizer displays efficient cell toxicity after photoexcitation. The distribution and action of THPTS in rat bladder caricinoma AY27 cells measured with fluorescence lifetime imaging microscopy shows accumulation of the THPTS in lysosomes and efficient cell death after irradiation. We found evidence that THPTS in water works mainly via the type I mechanism involving the reduction rather than oxidation of the excited triplet state THPTS(T1) via efficient electron donors in the biosystem environment and subsequent electron transfer to produce ROS indirectly. These intriguing structure-activity relationships may indeed open new strategies and avenues in developing PSs and PDT in general.