Objectives: The aim of this study was to investigate the cyto- and genotoxicity of nanocomposites (NCs) and generation of reactive oxygen species (ROS) as a result of particle-cell interactions. Materials and Methods: Titanium dioxide (TiO2-Ag) and ion-exchange resin (Res-Ag), both coated with silver (Ag), were examined. The murine macrophage J774A.1 cells were incubated in vitro with NC at different concentrations for 24 h. Cytotoxicity was analyzed by the methylthiazolyldiphenyltetrazolium bromide reduction test (MTT reduction test). ROS generation was assessed by incubation of cells with dichlorodihydrofl uorescein diacetate (DCF) and fl ow cytometry. DNA damage was detected by comet assay and included single-strand breaks (SSB), alkali-labile sites (ALS) and oxidative DNA damage after formamidopyrimidine glycosylase (FPG) treatment. The tail moment was used as an indicator of DNA damage. Results: TiO2-Ag was not cytotoxic up to 200 μg/ml, whereas IC50 for Res-Ag was found to be 23 μg/ml. Intracellular ROS levels were elevated after 4 h of exposure to Res-Ag at the concentration of 50 μg/ml. Both types of NC induced fragmentation of DNA strands, but only one of the composites caused damage to purine bases. TiO2-Ag induced SSB of DNA at concentrations of 10 and 5 μg/ml. For Res-Ag, a concentration-dependent increase in tail moments was observed. Conclusions: Silver-coated nanocomposites (both TiO2- Ag and Res-Ag) may cause genotoxic effects in murine macrophages J774A.1. Res-Ag increased generation of ROS which suggested that toxicity of Res-Ag in murine macrophages is likely to be mediated through oxidative stress. This paper will support industry and regulators alike in the assessment of hazards and risks and methods for their mitigation at the earliest possible stage in material and product development.