Few data are available about the effect of dimethylated forms (DMA) on aquatic organisms. As rarely a contaminant occurs alone, studies evaluating the combined effect of different contaminants in aquatic organisms are needed. In fact, the presence of nanomaterials, such as titanium dioxide nanoparticles (nTiO2), in the aquatic environment is now a reality due to its intensive production and use. So, this study evaluated the toxicological effects of DMA in an acute exposure condition and considered the potential influence of nTiO2 on the effects induced by DMA in the polychaete, Laeonereis culveri. The animals were exposed over 48 h to DMA (50 and 500 μg/l) alone or in combination with nTiO2 (1 mg/l). Biochemical parameters such as concentration of reactive oxygen species (ROS), glutathione-S-transferase (GST) activity, levels of reduced glutathione levels (GSH) and macromolecular (lipid and DNA) damage were evaluated, as well the DNA repair system. In addition, the accumulation of total As and the chemical speciation of the metalloid in the organisms was determined. The results showed that: (1) only the group exposed to 500 μg of DMA/l accumulated As and when co-exposed to nTiO2, this accumulation was not observed. (2) The levels of ROS increased in the group exposed to 50 μg/l of DMA alone and the effect was reversed when this group was co-exposed to nTiO2 (3) None of the treatments showed altered GST activity or GSH levels. (4) All groups that received nTiO2 (alone or in combination with DMA) showed lipid peroxidation. (5) The exposure to DMA (both concentrations) alone or in combination with nTiO2 induced DNA damage in L. culveri. These results showed that DMA exhibits a genotoxic effect and that co-exposure to nTiO2 had an influence on its toxicity. So the occurrence of both contaminants simultaneously can represent a threat to aquatic biota.