The present study examined the effect of titanium dioxide nanoparticles (nanoTiO2) and mercury (Hg) compounds on the green alga, Chlamydomonas reinhardtii. Mixtures containing nanoTiO2 of different primary sizes (5 nm, 15 nm and 20 nm), inorganic Hg (IHg) or monomethyl Hg (CH3Hg+, MeHg) were studied and compared with individual treatments. Oxidative stress and membrane damage were examined. Stability of nanoTiO2 materials in terms of hydrodynamic size and surface charge as well as Hg adsorption on different nanoTiO2 materials were characterized. The uptake of Hg compounds in the absence and presence of nanoTiO2 was also quantified. Results show that increasing concentrations of nanoTiO2 with different primary size diminished oxidative stress and membrane damage induced by high concentrations of IHg or MeHg, due to the adsorption of Hg on the nanoTiO2 aggregates and consequent decrease of cellular Hg concentrations. The observed alleviation effect of nanoTiO2 materials on Hg biouptake and toxicity was more pronounced for the materials with smaller primary size. IHg adsorbed onto the nanoTiO2 materials to a higher extent than MeHg. The present study highlights that the effects of contaminants are modulated by the co-existing engineered nanomaterials; therefore, it is essential to get a better understanding of their combined effect in the environment.