Nanoparticles have been drawn attention in various fields ranging from medicine to industry because of their physicochemical properties and functions, which lead to extensive human exposure to nano particles. Bismuth (Bi)-based compounds have been commonly used in the industrial, cosmetic and medical applications. Although the toxicity of Bi-based compounds was studied for years, there is a serious lack of information concerning their toxicity and effects in the nanoscale on human health and environment. Therefore, we aimed to investigate the toxic effects of Bi (III) oxide (Bi2O3) nanoparticles in liver (HepG2 hepatocarcinoma cell), kidney (NRK-52E kidney epithelial cell), intestine (Cato-2 colorectal adenocarcinoma cell), and lung (A549 lung carcinoma cell) cell cultures. Bi2O3 nanoparticles (similar to 149.1 nm) were easily taken by all cells and showed cyto- and genotoxic effects. It was observed that the main cell death pathways were apoptosis in HepG2 and NRK-52E cells and necrosis in A549 and Caco-2 cells exposed to Bi2O3 nanoparticles. Also, the glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy deoxyguanine (8-OHdG) levels were significantly changed in HepG2, NRK-52E, and Caco-2 cells, except A549 cell. The present study is the first to evaluate the toxicity of Bi2O3 nanoparticles in mammalian cells. Bi2O3 nanoparticles should be thoroughly assessed for their potential hazardous effects to human health and the results should be supported with in vivo studies to fully understand the mechanism of their toxicity. (C) 2016 Elsevier Ltd. All rights reserved.