The recent development of nanotechnology has facilitated a dramatic reduction in the size of materials. Nanomaterials are nanometer-sized materials with specific physicochemical properties that are different from those of the bulk material of the same composition. Such properties make them very attractive for cosmetic and medical applications. However, nanoparticles can act on living cells or bodies at the nano-level resulting in biologically undesirable as well as desirable effects. Thus, reduction in particle size from the micro- to nano-scale not only provides benefits to diverse scientific fields but also poses potential risks to the environment and to human health. Although significant resources are aimed at exploiting the desirable properties of nanoparticles for applications in medicine or cosmetics there are only limited attempts to evaluate potentially undesirable effects in vivo. Thus, there is a pressing need for a careful consideration of the benefits and side effects to the use of nanoparticles in medicine and cosmetics. In recent years, the majority of toxic biological response induced by nanomaterials (Nanotoxicity) has focused on cell culture systems. However, data from these studies will require verification from in vivo experiments using animals. An understanding of Toxicokinetics (the relationship between the physical properties of the nanomaterials and their in vivo behavior) would provide a basis for evaluating undesirable effects. Moreover, toxicoproteomics may identify predictive bio-markers for examining nanotoxicity. In this review article, we describe the assumptions and challenges in the field of nanotoxicity and describe advances for studying nanotoxicity of nanosilicas using toxicokinetics/toxicoproteomics both in vivo and in vitro.