The treatment depth of existing photodynamic therapy (PDT) is limited due to the absorption of the visible excitation light in biological tissue. It can be augmented by means of upconversion nanoparticles (UCNP) transforming deep-penetrating near-infrared (NIR) light to visible light, exciting PDT drugs. We report here a facile strategy to assemble such PDT nanocomposites functionalized for cancer targeting, based on coating of the UCNP with a silica layer encapsulating the Rose Bengal photosensitizer and bioconjugation to antibodies through a bifunctional fusion protein consisting of a solid-binding peptide linker (L) genetically fused to Streptococcus Protein G' (PG). The fusion protein (Linker-Protein G, LPG) mediates the functionalization of silica-coated UCNPs (UCNP@SiO2) with cancer cell antibodies allowing for specific target recognition and delivery. The resulting nanocomposites were shown to target cancer cells specifically, generate intracellular reactive oxygen species under 980-nm excitation, and induce NIR-triggered phototoxicity to suppress cancer cell growth in vitro.