Siliceous nanomaterials are attractive candidates for applications in cancer theranostics due to their precise synthesis control, ease of surface functionalization, accuracy of characterization, controllable release of cargo, and predictable pharmacokinetics. However, the inorganic silica core inherent to these nanomaterials has colloidal instability and can be cytotoxic, presenting notable challenges for their clinical translation. Surface coatings may be used to overcome this hurdle, by improving their stability, safety, and biological activity and thereby supporting their development for various biomedical applications. Out of the various surface coatings tested to date, lipid-based coatings have shown notable potential due to their biocompatibility and low immunogenicity, where lipids have demonstrated clinical success in the form of liposomal drug delivery systems. In this chapter, we will discuss lipid-coated siliceous nanomaterials, with an emphasis on the principles of lipid coating, the enhanced biocompatibility brought about by the lipid shell, and the use of lipid-coated silica nanoparticles in cancer therapy.