Abstract Structure toxicity relationship analysis was conducted using principal component analysis (PCA) for a panel of nanoparticles that included dry powders of oxides of titanium, zinc, cerium and silicon, dry powders of silvers, suspensions of polystyrene latex beads and dry particles of carbon black, nanotubes and fullerene, as well as diesel exhaust particles. Acute in vitro toxicity was assessed by different measures of cell viability, apoptosis and necrosis, haemolytic effects and the impact on cell morphology, while structural properties were characterised by particle size and size distribution, surface area, morphology, metal content, reactivity, free radical generation and zeta potential. Different acute toxicity measures were processed using PCA that classified the particles and identified four materials with an acute toxicity profile: zinc oxide, polystyrene latex amine, nanotubes and nickel oxide. PCA and contribution plot analysis then focused on identifying the structural properties that could determine the acute cytotoxicity of these four materials. It was found that metal content was an explanatory variable for acute toxicity associated with zinc oxide and nickel oxide, while high aspect ratio appeared the most important feature in nanotubes. Particle charge was considered as a determinant for high toxicity of polystyrene latex amine.