Abstract: Photodynamic therapy is a treatment mode that uses a specific wavelength of laser to excite photosensitizers to produce reactive oxygen species (ROS) to kill tumor cells. However, the half-life of ROS is very short and can only act to the close site of generation, which obviously limits the efficacy of photodynamic therapy. Organelles are the indispensable parts of cells that can work normally. For this reason, effective targeted delivery of photosensitizers to organelles is an effective strategy to improve the efficacy of photodynamic therapy. In this review, the design principles, targeting strategies, current challenges, and potential future directions of organelle-targeted photosensitizers will be introduced.