To investigate the possibility of removing titanium dioxide nanoparticles (TiO2 NPs) from water by coagulation, as well as to find the optimal coagulant and experimental conditions for TiO2 NP removal, four types of coagulant were adopted: polyferric sulfate (PFS), ferric chloride (FeCl3), polyaluminum chloride (PACl), and alum (Al2(SO4)3). It was found that the removal of TiO2 NPs by coagulation was affected by ionic strength, alkalinity, as well as types and dosages of coagulants. PFS and FeCl3 achieved much higher removal efficiency of TiO2 NPs than PACl and Al2(SO4)3 did. For 30 mg/L TiO2 NPs, a dosage of 0.3 mM PFS (as Fe) achieved 84% removal after coagulation followed by 30 min settlement. Optimal ionic strength (0.1 M NaCl or 0.03 M CaCl2) is of vital importance for the performance of PFS. Na2SO4 is unfavorable for the performance of PFS. Optimal alkalinity (0.01–0.03 M NaHCO3) is necessary for FeCl3 to remove TiO2 NPs. Natural organic matter, as represented by humic acid (HA) up to 11 mg/L, reduces the removal of TiO2 NPs by coagulation. These findings indicate that coagulation is a good option for the removal of TiO2 NPs from water, and more attention should be paid to the effects of water quality when using coagulation to remove TiO2 NPs from aqueous matrices. This provides a possible solution to alleviate the potential hazard caused by TiO2 NPs.