In　this　work,　a　novel　type　of　hollow　mesoporous　silica　nanoparticle　(HMSN)　with　a　rough　surface　has　been　successfully　prepared　via　a　facile　soft-hard　template　route　by　using　a　carbon　nanosphere　as　a　hard　template　and　cetyltrimethylammonium　bromide　(CTAB)　as　a　soft　template,　respectively.　This　method　involves　the　preparation　of　a　carbon　nanosphere,　sequential　coating　of　double　SiO2　layers,　and　the　removal　of　the　inner　carbon　core　and　CTAB　to　produce　HMSNs.　The　obtained　HMSNs　possess　spherical　morphology,　a　mesoporous　shell,　and　crumpled　surfaces.　The　controlled　experiments　prove　that　the　addition　of　3-ammonia　propyl　triethoxy　silane　(APTES)　is　very　crucial　for　the　formation　of　desired　HMSNs.　The　cell　tests　indicate　that　HMSNs　show　a　good　biocompatibility.　As　a　result,　the　potential　applications　of　HMSNs　are　further　explored　for　drug　delivery　and　protein　adsorption,　using　doxorubicin　hydrochloride　(DOX)　and　Cytochrome　c　(Cyt　c)　as　the　model　drug　and　protein,　respectively.　The　HMSNs　exhibit　high　drug　loading　and　protein　adsorption　capacity,　as　well　as　the　controlled　pH-responsive　release　behavior　for　DOX.　Therefore,　the　HMSNs　prepared　are　ideal　candidates　for　various　applications　such　as　nanoreactors,　drug　delivery　and　protein　adsorption.