The bioresponsive detection of DNA or proteins and the controlled release of drug molecules are two important research areas for both experimental studies and practical applications. However, the real incorporation of these two functions into one system is still untouched. Being different from the widely reported mesoporous silica nanoparticles that were used as the support, herein we report a smart system based on hybrid phosphonate-TiO(2) mesoporous nanostructures capped with fluorescein labeled oligonucleotides, which can realize simultaneous and highly-efficient biomolecule sensing and controlled drug release. The fluorescence of the labeled oligonucleotides is first quenched by the phosphonate-TiO(2) materials, which are related to the fluorescence resonance energy transfer mechanism. The addition of complementary DNA strands or protein target leads to the displacement of the capped DNA due to hybridization or protein-aptamer reactions. The opening of the pores can further cause the release of entrapped drugs as well as the restoration of dye fluorescence. The present method is proven to have high selectivity towards specific ssDNA and proteins.