Photodynamic　therapy　(PDT)　has　emerged　as　one　of　the　most　up-and-coming　non-invasive　therapeutic　modalities　for　cancer　therapy　in　rencent　years.　However,　its　therapeutic　effect　was　still　hampered　by　the　short　life　span,　limited　diffusion　distance　and　ineluctable　depletion　of　singlet　oxygen　(1O2),　as　well　as　the　hypoxic　microenvironment　in　the　tumor　tissue.　Such　problems　have　limited　the　application　of　PDT　and　appropriate　solutions　are　highly　demand.　Methods:　Herein,　a　programmatic　treatment　strategy　is　proposed　for　the　development　of　a　smart　molecular　prodrug　(D-bpy),　which　comprise　a　two-photon　photosensitizer　and　a　hypoxia-activated　chemotherapeutic　prodrug.　A　rhodamine　dye　was　designed　to　connect　them　and　track　the　drug　release　by　the　fluorescent　signal　generated　through　azo　bond　cleavage.　Results:　The　prodrug　(D-bpy)　can　stay　on　the　cell　membrane　and　enrich　at　the　tumor　site.　Upon　light　irradiation,　the　therapeutic　effect　was　enhanced　by　a　stepwise　treatment:　(i)　direct　generation　of　1O2　on　the　cell　membrane　induced　membrane　destruction　and　promoted　the　D-bpy　uptake;　(ii)　deep　tumor　hypoxia　caused　by　two-photon　PDT　process　further　triggered　the　activation　of　the　chemotherapy　prodrug.　Both　in　vitro　and　in　vivo　experiments,　D-bpy　have　exhabited　excellent　tumor　treatment　effect.　Conclusion:　The　innovative　programmatic　treatment　strategy　provides　new　strategy　for　the　design　of　follow-up　anticancer　drugs.