Red blood cells (RBCs) have been widely explored as a naturaldrug delivery system (DDS) owing to their inherent biocompatibility and largeinternal cavities to load various types of functional molecules. Herein, we uncover that a photosensitizer, chlorin e6 (Ce6), could be decorated into themembrane of RBCs upon simple mixing, without affecting the membraneintegrity and stability in dark. Upon light irradiation with a rather low powerdensity, the singlet oxygen generated by Ce6 would lead to rather efficientdisruption of RBC membrane. With doxorubicin (DOX), a typicalchemotherapy drug, as the model, we engineer a unique type of light responsive RBC-based DDS by decorating Ce6 on the cell membrane andloading DOX inside cells. The light triggered cell membrane breakdown wouldthus trigger instant release of DOX, enabling light-controlled chemotherapywith great specificity. Beyond that our RBC system could also be utilized for loading of larger biomolecules such as enzymes, whose release as well as catalytic function is also controlled by light. Our workthus presents a unique type of biocompatible cell-based DDS that can be precisely controlled by mild external stimuli, promisingnot only for cancer therapy but also for other potential applications in biotechnologies.