Photosensitizers played crucial roles in photodynamic therapy (PDT) and most of them owned the macrocyclic and conjugated structures, which would lead to undesired aggregation-induced quenching (ACQ) effect. To solve the ubiquitous ACQ effect and strong hydrophobicity of photosensitizers, in this work, a series of water-soluble polyporphyrins (P-1O, P-3O, and P-5O) were prepared using different flexible chains containing ether groups. Upon screening, P-5O owned best water-solubility, highest singlet oxygen yield (1.95 folds vs porphyrin monomer), and could self-assembled into nanoparticles (NPs) with the particle size of 100 nm in a carrier-free manner. Such NPs had excellent stability upon different pH values, serum, dilution folds, freeze-drying, and incubation time. In vitro photo/dark toxicity results indicated that the NPs had low dark-toxicity in both tumor cells (Hep1-6) and normal cells (293T) (cell viability higher than 80%). The NPs had obvious photo-toxicity in Hep1-6 cells(cell viability fewer than 30%), indicating the typical anti-cancer PDT effect.