A one-step method for continuous large-scale synthesis of well-defined hollow titania spheres was established by feeding titanium tetrachloride mixed with ethanol vapor to a facile diffusion fiame. A mixture of TiCl4 and C2H5OH vapor was transported at 100 m/s into a fiame reactor and condensed into mesoscale droplets due to Joule-Thomson cooling and the entrainment of cool gases into the expanding high-speed jet. Hollow crystalline TiO2 spheres with good thermal stability were formed after the hydrolysis of TiCl4 in the H2/air fiame at about 1500 fiC. Structural characterization indicates that the hollow spheres, with uniform diameter of 300 nm and shell thickness of 35 nm, consist of 20-30 nm TiO2 nanocrystallites. A formation mechanism of the hollow spheres was proposed, involving the competition between chemical reaction and diffusion during the fiame process. The present study provides a new pathway for continuous and large-scale engineering of hollow nanomaterials. A one-step method for continuous large-scale synthesis of well-defined hollow titania spheres was established by feeding titanium tetrachloride mixed with ethanol vapor to a facile diffusion fiame. A mixture of TiCl4 and C2H5OH vapor was transported at 100 m / s into a floromethane and condensed into mesoscale droplets due to Joule-Thomson cooling and the entrainment of cool gases into the expanding high-speed jet. Hollow crystalline TiO2 spheres with good thermal stability formed after the hydrolysis of TiCl4 in the H2 / air fiame at about 1500 fiC. Structural characterization indicates that the hollow spheres, with uniform diameter of 300 nm and shell thickness of 35 nm, consisting of 20-30 nm TiO2 nanocrystallites. A formation mechanism of the hollow spheres was proposed, involving the competition between chemical reaction and diffusion present the fiame process. The present study provides a new pathway for continuous and large-scale engineering of hollow nanomaterials.