The development of new methods which enable exquisite control over crystal size over a wide range is highly desired for optimizing their performance. In this work, we employed anatase TiO2 as an example to demonstrate a heterogeneous nucleation approach by coupling the slow hydrolysis of a titanium precursor and a dispersible silica substrate. After tight control of the number of nucleation sites, the crystal size is greatly dependent on the number of seeds. An in-depth nucleation analysis was carried out that showed that the reaction product, hydrofluoric acid (HF), plays a key role in selective etching of the substrate and further leads to crystal–substrate separation. Additionally, our preliminary results illustrated that the growth of Fe2O3 crystals can also be tuned by such a method without shape and composition variation. To the best of our knowledge, this is the first report of fine-tuning the crystal size of anatase TiO2 by a heterogeneous nucleation method, and this provides a promising way to design and synthesize new materials with appropriate size and shape.