Nowadays, protein therapeutics receive unprecedented recognition for their great potential in the treatment of a variety of diseases. The efficacy of native therapeutic proteins is limited by their intrinsic poor stability and cell membrane permeability. Tremendous efforts have been devoted to developing efficient protein delivery systems. The past decade has witnessed the development and successful application of silica-based nanoparticles (SiNPs) as therapeutic protein carriers. This review focuses on recent advances in SiNPs in therapeutic protein delivery for disease and cancer treatment. The limitations of current studies and the room for improvement of SiNPs in therapeutic protein delivery are discussed.