The effect of energy input, pH and temperature on de-aggregation of hydrophilic silicon dioxide powder (particle size 12 nm) in a high shear mixer was investigated. It has been found that de-aggregation is a two step process. Initially, at low energy input very large aggregates (3–1000 μm) are gradually broken into smaller secondary aggregates (2–100 μm) of a single modal size distributions. As the energy input increases primary aggregates (0.03–1 μm) are eroded from the secondary aggregates leading to bimodal size distributions with the first mode between 0.03 μm and 1 μm corresponding to the primary aggregates and the second mode between 2 μm and 100 μm corresponding to the secondary aggregates. At a sufficiently high energy density all secondary aggregates are broken into primary aggregates however, even at the highest energy density employed the primary aggregates could not be broken into single nano-particles. The temperature and the pH affect de-aggregation kinetics but do not alter de-aggregation pattern. Increasing pH at low temperature speeds up de-aggregation, whilst increasing pH at high temperature slows down de-aggregation process.