Nanostructured anatase TiO2 undergoes pressure-induced phase transformation, and the transformation sequence is significantly different from the bulk counterpart. The size and the morphology are found both playing a critical role in the phase transformation behavior. In this work, we prepare anatase TiO2 microspheres using a hydrothermal method. By controlling the reaction time, hollow and solid spheres of similar diameters are prepared. TEM and XRD analysis reveals that these microspheres are aggregates of anatase nanocrystalline of size between 15–16 nm. The phase transformation behaviour under high temperature is examined in situ using both Raman spectroscopy and synchrotron x-ray diffraction. We find that although both solid and hollow spheres are micron-sized, they undergo phase transformation sequence similar to nanomaterials with size of several tens of nanometers. Hollow spheres exhibit a higher compressibility than the solid spheres. A detailed analysis based on the formation mechanism of the spheres is performed to explain the unique phase transformation behavior of these materials.