Nanoparticles are concerned to show adverse biological effects despite their unique functions. Their physicochemical properties and status are widely diverse; this makes safety analysis of nanoparticles complicated. Some reports showed that nanoparticles could disturb acquired immunity, while it is still unclear what is the inducer of that effects. Here, we tried to explore the relationship among nanoparticles' physicochemical properties and sensitizing potential by using the human cell line activation test based in vitro method; that uses in expression of CD86 and CD54 as an index of cellular activation. As a model of nanoparticles, we examined sensitization potential of silica particles with or without a human protein corona. Of the cells treated with silica particles (diameter: 50 or 300 nm) only, none of them showed activation. On the other hand, silica particles with human protein corona showed activation. Moreover, protein corona that forms around 50 nm silica nanoparticles have a higher sensitization potential than that of protein corona that forms around 300 nm silica particles. Our findings indicated that silica particles with human protein corona showed sensitization potential, and that sensitization potential could depend on the amount or kind of proteins within the corona.