In this study, silica nanoparticle was synthesised and used to promote lysozyme crystallisation effectively against high concentrations of protein impurity (bovine serum albumin (BSA); concentration = 25.0–50.0 mg/mL vs 5.0–25.0 mg/mL for lysozyme) at 1 mL scale, demonstrating that crystallisation is a viable and scalable protein purification technology with the aid of heterogeneous nucleants. The silica nanoparticle expedited the crystallisation of lysozyme through the enhancement of nucleation, significantly improving the process productivity. Furthermore, this study demonstrates the proper use of nanoparticle in terms of process time, as the improvement of product recovery by silica nanoparticle has a monomodal peak shape over time.