The stability and bioavailability of titanium dioxide nanoparticles (TiO 2 NPs) suspension could be modified by the physicochemical properties of solution. In the present study, the effect of humic acid (HA) and ionic strength (by adding NaCl) on aggregation and sedimentation of TiO 2 NPs suspension were investigated. Accordingly, the sublethal toxicity of TiO 2 NPs suspensions with different HA and NaCl concentrations toward zebrafish (Danio rerio) was evaluated by monitoring the changes of superoxide dismutase, catalase, malonaldehyde and glutathione in gill, liver and intestine. The results showed that the aggregations formation and hydrodynamic diameter of TiO 2 NPs in suspensions are not essential characteristics to decide toxicity. The varied oxidative stress responses detected in gill, liver and intestine derived from different toxicity mechanisms of TiO 2 NPs. Nevertheless, the oxidative stress could be suppressed by the adding of HA and/or the increase of ionic strength, which can decrease the bioavailability of TiO 2 NPs in water. The study suggests that the environmental factors, such as HA and ionic strength, are important for the fate (aggregation and sedimentation) and toxicity of nanomaterials in aquatic environment.