Well-dispersed hollow TiO2 spheres were synthesized via Ostwald ripening through a fluorine-free solvothermal process in a n-PrOH/H2O mixed solvent. Several commonly used acids, such as HNO3, HCl, and H2SO4, were found to be effective as the ripening-directing agent to replace the highly corrosive HF, and the hollow TiO2 sphere size could be modulated by varying the reactant concentrations. The effects of the solvents and reactants were explored in details, which demonstrated that four important criteria existed in this fluorine-free process to create well-dispersed hollow TiO2 spheres, including the utilization of n-PrOH/H2O mixed solvent, certain degree of acidity, coexistence of different acids, and the existence of SO42 in the reaction solution. After calcination for a better crystallization, these hollow TiO2 spheres were composed of pure anatase phase, and had a good photocatalytic degradation performance on RhB under UV illumination.