A type of novel hypocrellin B gelatin nanoparticles (HB-G-NP), with size of 20-200 nm, was prepared and characterized. The nanoparticles are readily soluble in water or phosphate-buffered saline (PBS). The interaction between HB-G-NP and a fluorescence protein, C-phycocyanin (C-PC) from Spirulina platensis, was studied. It was found that the energy transfer from HB to C-PC was quite efficient, suggesting adsorption of C-PC on surface of the nanoparticles; secondly, the photosensitization of HB resulted in not only the photo-damage of C-PC but also the photobleaching of HB in the presence of oxygen while it did not in the absence of oxygen, suggesting that the movable reactive oxygen species, instead of the immovable anionic radicals of the photosensitizer, should be responsible for the photo-induced processes. Considering the short free diffusion path length of the reactive oxygen species, it can be deduced that smaller or ring-like particles should be more effective for photo-damage of biomolecules or target tissues.