The increasing use of engineered nanoparticles in industrial and consumer products leads to a release of the anthropogenic contaminants to the aquatic environment. To obtain a better understanding of the environmental effects of these particles, the nematode Caenorhabditis elegans was used to investigate the organism-level effects and in vivo molecular responses. Toxicity of bulk-scale (∼160 nm) and nanoscale (21 nm) titanium dioxide (TiO2 ) was tested under dark and light conditions, following ISO 10872. The expression of sod-3, a mitochondrial superoxide dismutase, was quantified as an indicator for oxidative stress induced by the photocatalytically active material. Particle sizes were estimated using dynamic light scattering and scanning electron microscopy. Although both materials agglomerated to a comparable secondary particle size of 300 nm to 1500 nm and were ingested into the intestine, only nanoscale-TiO2 significantly inhibited reproduction (lowest-observed-effect-concentration [LOEC]: 10 mg/L). Light exposure induced the production of reactive oxygen species (ROS) by nanoscale-TiO2 and increased toxicity of the nanomaterial from a median effect concentration of more than 100 mg/L to 53 mg/L. No evidence was found for inner cellular photocatalytic activity of nanoscale-TiO2 . Therefore, oxidative damage of the membranes of intestinal cells is suggested as a potential mode of action. Results highlight the importance of primary particle size and environmental parameters on the toxicity of TiO2 .