Titanium dioxide (TiO2) based nanomaterials (NMs) are among the most produced NMs worldwide. When irradiated with light, particularly UV, TiO2 is photoactive, a property that is explored for several purposes. There are an increasing number of reports on the negative effects of photoactivated TiO2 on non-target organisms. We have here studied the effect of a suite of reference type TiO2 NMs (i.e. NM103, NM104, and NM105 and compared these to the bulk) with and without UV radiation to the oligochaete Enchytraeus crypticus. High-throughput gene expression was used to assess the molecular mechanisms, while also anchoring it to the known effects at the organism level (i.e., reproduction). Results showed that the photoactivity of TiO2 (UV exposed) played a major role in enhancing TiO2 toxicity, activating the transcription of oxidative stress, lysosome damage and apoptosis mechanisms. For non-UV activated TiO2, where toxicity at the organism level (reproduction) was lower, results showed potential for long-term effects (i.e., mutagenic and epigenetic). NM specific mechanisms were identified: NM103 affected transcription and translation, NM104_UV negatively affected the reproductive system/organs, and NM105_UV activated superoxide anion response. Results provided mechanistic information on UV-related phototoxicity of TiO2 materials and evidence for the potential long-term effects.