Abstract Besides their economic value, engineered inorganic nanoparticles (EINPs) may pose a risk for the integrity of ecosystems. Among EINPs, titanium dioxide (nTiO 2) is frequently used and released into surface waters in the μg range. There, nTiO 2 interacts with environmental factors, influencing its potential to cause adverse effects on aquatic life. Although factors like ultra violet (UV) light and natural organic matter (NOM) are considered as ubiquitous, their joint impact on nTiO 2 -induced toxicity is poorly understood. This study addressed the acute toxicity of nTiO 2 (P25; 0.00–64.00 mg/L; ~60 nm) at ambient UV light (0.00–5.20 W UVA/m2) and NOM levels (seaweed extract; 0.00–4.00 mg TOC/L), using the immobility of Daphnia magna as response variable. Confirming previous studies, effects caused by nTiO 2 were elevated with increasing UV radiation (up to ~280 fold) and mitigated by higher NOM levels (up to ~12 fold), possibly due to reduced reactive oxygen species (ROS; measured as •OH radicals) formation at lower UV intensities. However, contradicting to former studies, nTiO 2 -mediated ROS formation was not proportional to increasing NOM levels: lower concentrations (0.04–0.40 mg TOC/L) slightly diminished, whereas a higher concentration (4.00 mg TOC/L) promoted the ROS quantity, irrespective of UV intensity. Measured ROS levels do not fully explain the observed nTiO 2 -induced toxicity, whereas increasing acetylcholinesterase and glutathione-S-transferase activities in daphnids (in presence of 8.00 mg/L nTiO 2 and elevated UV intensity) point towards neurotoxic and oxidative stress as a driver for the observed effects. Hence, despite higher •OH levels in the treatments where 4.00 mg TOC/L were present, NOM was still capable of reducing nTiO 2 -induced stress and ultimately adverse effects in aquatic life. Graphical abstract Unlabelled Image Highlights • Environmental parameters meaningfully modify nanoparticle toxicity. • UV light enhances the toxicity of titanium dioxide nanoparticles. • Natural organic matter increases ROS formed by titanium dioxide. • Oxidative stress and acute toxicity are reduced by natural organic matter. • Adverse nanoparticle effects potentially at predicted environmental concentrations. [ABSTRACT FROM AUTHOR]