Photoactivated perylenequinones are photosensitizers that transfer into reactive oxygen species with light energy for photodynamic therapy (PDT). Novel photoactivated perylenequinones photosensitizers are of current interest for application in PDT. Cercosporin, a new photoactivated perylenequinone photosensitizer, was encapsulated into multifunctional copolymer for targeting hepatocellular carcinoma cells to give enhanced PDT efficiency. The cercosporin encapsulated multifunctional copolymer exhibited higher targeting ability and better PDT efficiency to HepG2 cells compared with non-targeting copolymer system. Z-stack technique was used to monitor the cytoplasm distribution of cercosporin. The multifunctional copolymer can release cercosporin only in acidic tumor microenvironment to induce a PDT effect and realize the tracking ability thanks to covalent binding with rhodamine B. The cercosporin encapsulated multifunctional copolymer holds great potential in PDT for cancer treatment.