Aquatic organisms are exposed to mixtures of environmental pollutants, including engineered nanoparticles; however, the interactions underlying cocktails’ effects are poorly understood, in particular, the kinetic aspects. The present study explored the time course of the interactions between nano-sized titanium dioxide (nTiO2) with different primary particle sizes, algae and inorganic mercury (Hg) over 96 h under conditions that were representative of a highly contaminated environment. The results showed that nTiO2 with smaller primary particle size and higher concentrations rapidly reduced the adsorption and internalization of mercury by green alga Chlamydomonas reinhardtii. Such a mitigating effect on mercury bioavailability could be explained by the strong adsorbing capacity of nTiO2 for Hg and the aggregation and sedimentation of nTiO2 and bound Hg. The present study highlighted the key processes determining the bioavailability of mercury to the algae in mixture exposure under conditions representative of a highly contaminated environment, such as industrial wastewater effluents.