The hierarchically structured core-shell magnetic mesoporous silica nanospheres (Mag-MSNs) have attracted extensive attention, particularly in studies involving reliable preparations and diverse applications of the multifunctional nanomaterials in multi-disciplinary fields. Intriguingly, Mag-MSNs have been prepared with well-designed synthesis strategies and used as adsorbent materials, biomedicines, and in proteomics and catalysis due to their excellent magnetic responsiveness, enormous specific surface area and readiness for surface modifications. Through a carefully designed surface modification of Mag-MSNs, the performance and application prospects of the material are greatly improved. Typically, the introduction of various molecular matrices into the shell of Mag-MSNs facilitates the combination of surface modifications and magnetic separation technology. So far, as sustainable chemistry is concerned, it is important to recover the functionalized core-shell Mag-MSNs after the reaction and reuse them without losing activity. In this review, the design conceptions and the construction of core-shell Mag-MSNs are discussed. Furthermore, various surface modification approaches of core-shell Mag-MSNs are summarized, and recent applications of these functionalized nanomaterials in the fields of biomedicine, catalysis, proteomics and wastewater treatment are exemplified. 2 3 4 5 6 7 8