AbstractPhotolysis has enabled the occurrence of numerous discoveries in chemistry, drug discovery and biology. However, there is a dearth of efficient long wavelength light mediated photolysis. Here, we report general and efficient long wavelength single photon method for a wide array of photolytic molecules via triplet-triplet annihilation photolysis. This method is versatile and “LEGO”-like. The light partners (the photosensitizers and the photolytic molecules) can be energetically matched to adapt to an extensive range of electromagnetic spectrum wavelengths and the diversified chemical structures of photoremovable protecting groups, photolabile linkages, as well as a broad array of targeted molecules. Compared to the existing photolysis methods, our strategy of triplet-triplet annihilation photolysis not only exhibits superior reaction yields, but also resolves the photodamage problem, regardless of whether they are single photon or multiple photon associated. Furthermore, the biological promise of this “LEGO” system was illustrated via developing ambient air-stable nanoparticles capable of triplet-triplet annihilation photolysis.