Porphyrins are vital pigments involved in biological energy transduction processes. Their abilities to absorb light, then convert it to energy, have raised the interest of using porphyrin nanoparticles as photosensitizers in photodynamic therapy. A recent study showed that self- assembled porphyrin-silica composite nanoparticles can selectively destroy tumor cells, but detection of the cellular uptake of porphyrin-silica composite nanoparticles was limited to imaging microscopy. Here we developed a novel method to rapidly identify porphyrin-silica composite nanoparticles using Atmospheric Solids Analysis Probe-Mass Spectrometry (ASAP-MS). ASAP-MS can directly analyze complex mixtures without the need for sample preparation. Porphyrin-silica composite nanoparticles were vaporized using heated nitrogen desolvation gas, and their thermo-profiles were examined to identify distinct mass- to-charge (M/Z) signatures. HeLa cells were incubated in growth media containing the nanoparticles, and after sufficient washing to remove residual nanoparticles, the cell suspension was loaded onto the end of ASAP glass capillary probe. Upon heating, HeLa cells were degraded and porphyrin-silica composite nanoparticles were released. Vaporized nanoparticles were ionized and detected by MS. The cellular uptake of porphyrin-silica composite nanoparticles was identified using this ASAP-MS method.