TiO2 hollow spheres with controllable size were successfully synthesized through a hydrothermal silica etching method; SiO2 cores were easily removed without the use of a toxic reagent. The parameters for the synthesis of SiO2 cores and TiO2 hollow spheres, including stirring time, ammonia concentration, tetrabutyl titanate content, hydrothermal time, and reflux time, were systematically investigated. SiO2 cores and TiO2 hollow structure were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray spectra (EDX), X-ray photoelectron spectroscopy (XPS), and N-2 adsorption-desorption isotherms. The results revealed that the mean diameter of SiO2 was similar to 280 nm when the concentration of ammonia was 4.8 M and the stirring time was 0.5 h. For hollow TiO2, when the operation process was optimized (ammonia volume 0.35 mL, TBOT addition 1.5 mL, hydrothermal time 3 h, and reflux time 3 h), the average size and the shell thickness were 270 and 100 nm, respectively. The process exhibited a high drug loading capacity (33.12 +/- 0.01%) and encapsulation rate (99.03 +/- 0.24%) due to its high specific surface area of 121.62 m(2).g(-1). In addition, TiO2 hollow spheres displayed pH-responsive sustained-controlled drug release behavior in vitro which released 80% of doxorubicin at 5.0 pH within 120 h, its release kinetic showed that it fits well with Zero-order kinetic equation, demonstrating that DOX center dot HCl/hollow TiO2 maintains constant release rate, and the investigation of blood compatibility showed that the hemolysis rate of hollow TiO2 did not exceed 3% in the concentration range of 100 and 4000 mu g/mL, further confirming that prepared hollow TiO2 is a relatively safe medical inorganic material. (C) 2019 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.