Mesoporous　silica　nanoparticles　(MSN)　based　controlled　release　system　had　been　coupled　with　diverse　detection　technologies　to　establish　biosensors　for　different　targets.　Chemiluminescence　(CL)　system　of　luminol/H2O2　owns　the　characters　of　simplicity,　low　cost　and　high　sensitivity,　but　the　targets　of　which　are　mostly　focused　on　some　oxidants　or　which　can　participate　in　a　chemical　reaction　that　yields　a　product　with　a　role　in　the　CL　reaction.　In　this　study,　chemiluminescent　detection　technique　had　been　coupled　with　mesoporous　silica-based　controlled　released　system　for　the　first　time　to　develop　a　sensitive　biosensor　for　the　target　which　does　not　cause　effect　to　the　CL　system　itself.　Cocaine　had　been　chosen　a　model　target,　the　MSN　support　was　firstly　loaded　with　glucose,　then　the　positively　charged　MSN　interacted　with　negatively　charged　oligonucleotides　(the　aptamer　cocaine)　to　close　the　mesopores　of　MSN.　At　the　present　of　target,　cocaine　binds　with　its　aptamer　with　high　affinity;　the　flexible　linear　aptamer　structured　will　become　stems　structured　through　currently　well-defined　non-Waston-Crick　interactions　and　causes　the　releasing　of　entrapped　glucose　into　the　solution.　With　the　assistant　of　glucose　oxidase　(GOx),　the　released　glucose　can　react　with　the　dissolved　oxgen　to　produce　gluconic　acid　and　H2O2,　the　latter　can　enhance　the　CL　of　luminol　in　the　NaOH　solution.　The　enhanced　CL　intensity　has　a　relationship　with　the　cocaine　concentration　in　the　range　of　5.0-60μM　with　the　detection　limit　of　1.43μM.　The　proposed　method　had　been　successfully　applied　to　detect　cocaine　in　serum　samples　with　high　selectivity.　The　same　strategy　can　be　applied　to　develop　biosensors　for　different　targets.　©　2015　Elsevier　B.V.