The　clinical　administration　of　biophotonic　approaches,　such　as　photodynamic　therapy　(PDT),　is　impeded　by　the　low　penetration　of　visible　light　in　biological　tissues.　The　cooperation　of　infrared　(IR)　light　with　deeper　penetration　and　implantable　IR-to-visible　upconversion　materials　and　devices　establishes　an　effective　strategy　to　generate　visible　light　in　deep　tissue.　In　this　work,　a　wirelessly　powered　upconversion　waveguide-based　light　source　is　reported　for　PDT-based　in　vivo　cancer　treatments　in　deep　tissue.　Combining　microscale　IR-to-visible　upconversion　device　arrays　and　a　biocompatible　waveguide,　the　implant　exhibits　enhanced　IR　transmission　in　biological　environments　and　generates　upconverted　red　emission　in　the　target　region　at　a　depth　＞10　mm.　The　red　illumination　activates　a　photosensitizer　in　5-aminolevulinic　acid　(5-ALA)-based　PDT　treatment,　inducing　massive　apoptosis　(＞60%　cell　death)　of　tumor　cells.　After　implanted　in　tumor-bearing　mice,　the　waveguides　enable　chronic　operation　for　more　than　two　weeks　and　reveal　ideal　anti-tumor　efficacies　in　the　PDT　process.　Finally,　the　biocompatible　waveguide　can　be　retrieved　from　the　tissue,　leaving　minimal　traces　after　treatments.　Such　a　waveguide　implant　represents　a　prospective　technique　to　realize　optical-based　biological　modulations　and　medical　treatments　within　the　body.