Nanoparticles are gaining much importance for biological application in biomedicine, biotechnology and other life sciences. For their unique physicochemical properties they are used in molecular diagnostics, cancer therapy, as well as drug and gene delivery systems. Among all nanoparticles, silver ones (AgNPs) have the highest degree of commercialization. For their strong antimicrobial, antiviral and antifungal activity, they have been used extensively in a range of medical settings especially in wound dressings. Nanoparticles are defined as structures that have at least one dimension in 1-100 nm range. Their ultra-small size in comparison to enormous surface area, makes AgNPs very reactive forms. Small size also affirms grate particles mobility and has impact on their cellular distribution. Depending on the size, shape and the type of a carrier, AgNPs demonstrate different physicochemical properties. This study was undertaken to examine the potential toxicity effects of 15 nm PVP-coated AgNPs on Normal Human Primary Keratinocytes (NHEK). Cells were treated with different concentrations of AgNPs and then cell viability, morphology and metabolic activity were studied. To determined a role of AgNPs in signal transduction pathway, we examined an activation of several proteins involved in cell response to extracellular factors. We observed that 15 nm PVP-coated AgNPs decreased cell viability, metabolic activity, as well as they caused inhibition of cells proliferation and migration. Moreover, they induced DNA damage and increased caspase 3/7 activity. AgNPs significantly activated p38 MAPK, as well as caused weak activation of Erk 1/2 kinase and p53 protein. AgNPs increased level of mRNA coding for pro-apoptotic proteins from Bcl-2 family, as Bax and Puma. Used nanoparticles have a toxic impact on NHEK cells and they are acting in time- and/or dose-dependent manner. Our studies show, that despite the positive effects, AgNPs may present possible danger, concerning activation of genotoxic and cytotoxic processes.