Titanium dioxide nanoparticles (nTiO2) are expected to interact with natural substances and other chemicals in the environment, however little is known about their combined effects. Therefore, this study assessed the toxicity of copper (Cu) in combination with varying crystalline phases (anatase, rutile, and the mixture) of nTiO2 and differing organic materials on Daphnia magna. The nanoparticles reduced the Cu-toxicity depending on the product (0.3- to 2-fold higher 48-h EC50). This decrease in toxicity coincided with a lowered Cu-concentration in the water column, which was driven by the adsorption of Cu to nTiO2-depending on available surface area and structure-and their subsequent sedimentation. In the presence of organic material and nTiO2, the Cu-toxicity was further reduced (up to 7-fold higher 48-h EC50). This observation can be explained by a reduced Cu-bioavailability as a result of complexation and adsorption by the organic material and nTiO2, respectively. Thus, the crystalline phase composition, which is determining the surface area and structure of nTiO2, seems to be of major importance for the toxicity reduction of heavy metals, while the influence of the organic materials was mainly driven by the quantity and quality of humic substances.