The　mesoporous　SiO2/dense　SiO2/Fe3O4　multiply　coated　hollow　microspheres　were　prepared　by　a　multistep　coating　technique.　At　first,　the　dense　SiO2　layers　with　the　thickness　of　4.2　nm　were　coated　on　the　Fe3O4　nanorods　to　prevent　them　from　being　corroded　in　acidic　system.　Then,　the　mesoporous　SiO2　was　coated　on　the　composite　microspheres　via　a　sol-gel　and　hydrothermal　synthesis　process　by　using　TEOS　as　silicon　source,　P123　in　combination　with　co-surfactant　CTAB　as　template　in　acidic　system.　The　mesoporous　SiO2/dense　SiO2/Fe3O4　multiply　coated　hollow　microsphere　has　a　narrow　pore　size　distribution　around　3.74　nm,　a　large　surface　area　of　505　m(2)　g(-1),　and　a　pore　volume　of　0.47　cm(3)　g(-1).　The　composite　microspheres　had　a　high　papain　immobilization　(222　mg/g)　since　the　hollow　cavity　in　the　composite　microsphere　is　a　natural　warehouse　storing　papain　molecules　effectively.　The　pH　stabilities　and　temperature　stabilities　of　the　immobilized　papain　activity　were　much　higher　than　that　of　the　free　papain　activity.　(C)　2016　Published　by　Elsevier　B.V.