Aptamer-or　antibody-based　sensing　protocols　have　been　reported　for　detecting　carcinoembryonic　antigen　(CEA),　but　most　exhibit　complicated　procedures　or　multiple　reactions.　In　this　work,　we　developed　a　one-step　aptasensing　protocol　for　the　spectrometric　determination　of　CEA　based　on　4-nitrophenol　(4-NP)-loaded　magnetic　mesoporous　silica　nanohybrids　(MMSNs)　for　bioresponsive　controlled-release　applications.　To　fabricate　such　a　responsive–controlled　sensing　system,　single-stranded　complementary　oligonucleotides　relative　to　the　CEA-specific　aptamer　were　first　modified　on　the　aminated　MMSN.　Thereafter,　4-NP　molecules　blocked　the　pores　with　the　assistance　of　the　aptamers　via　a　hybridization　reaction.　The　introduced　target　CEA　specifically　reacted　with　the　hybridized　aptamer,　thus　detaching　from　the　MMSN　to　open　the　gate.　The　loaded　4-NP　molecules　were　released　from　the　pores,　as　determined　using　ultraviolet–visible　(UV–vis)　absorption　spectroscopy　after　magnetic　separation.　Under　optimum　conditions,　the　absorbance　increased　with　an　increase　in　the　target　CEA　in　the　sample　and　exhibited　a　good　linear　relationship　within　the　dynamic　range　of　0.1–100　ng　mL−1,　with　a　detection　limit　of　46　pg　mL−1.　Moreover,　this　system　also　displayed　high　specificity,　good　reproducibility,　and　acceptable　accuracy　for　analyzing　human　se-rum　specimens,　in　comparison　with　a　commercialized　human　CEA-enzyme-linked　immunosorbent　assay　(ELISA)　kit.　©　2021　by　the　authors.　Licensee　MDPI,　Basel,　Switzerland.