The aim of our study was to evaluate the effects of gold (Au) and silver (Ag) nanoparticles (NPs) at different concentrations on cultured human osteoarthritic chondrocytes. Cell viability and inducible nitric oxide synthase expression were evaluated by light microscopy. Using transmission electron microscopy (TEM) and field emission gun-based scanning transmission electron microscopy/energy dispersive spectroscopy (FEG-STEM/EDS) allowed us to localize NPs. Gene expression of matrix metalloproteinases 1, 3 and 13 and A disintegrin and metalloproteinase with thrombospondin motifs -4 and -5 were carried out by real-time polymerase chain reaction. A cell viability test indicated a significant dose-dependent cytotoxic effect of both NPs. At concentrations of 160 and 250 μM NP light microscopy showed chondrocytes with signs of apoptosis and an increased presence of inducible nitric oxide synthase. Au-NPs were characterized by FEG-STEM/EDS and TEM analysis localized NPs in cytoplasm and in endocytotic vesicles. On the contrary, the Ag-NPs were undetectable by FEG-STEM/EDS and TEM. Increased gene expression, particularly in matrix metalloproteinase-3, was observed for both NPs (160 μM), but at a concentration of 250 μM the expression of the evaluated genes became lower. Our in vitro studies, although preliminary, suggest that engineered Au and Ag-NPs appear to be harmful for human osteoarthritic chondrocytes in high concentrations (160–250 μM). Copyright © 2013 John Wiley & Sons, Ltd.