<p>The precise detection of microRNAs (miRNAs) in tumor tissue is vital for the early diagnosis of cancer. In this work, we propose an electrochemiluminescence (ECL) aptasensing strategy for the sensitive detection of miRNA-122 in living cancer cells. To tremendously amplify the ECL response, a zinc-porphyrin-organic framework embraced with ZnO nanoparticles (NPs), which was synthesized through solvothermal synthesis using 5,10,15,20-tetra(4-pyridyl)porphyrin (TPyP) as linking ligand and zinc nitrate as precursor (represented by Zn-TPyP@ZnO), simultaneously served as bioplatform and ECL emitter in the presence of the coreactant K₂S₂O₈. The generation of a microinterface between Zn-TPyP and ZnO NPs endowed fast electron transfer, improved catalytic performance, and superior biocompatibility. These advantages of the Zn-TPyP@ZnO heterojunction confers the system with strong reduction capability toward S₂O₈²⁻ to generate SO₄^•− and toward O₂ to produce O₂^•− or •OH, as well as excellent anchoring capability for the miRNA-122-targeted aptamer. Therefore, the developed Zn-TPyP@ZnO-based ECL aptasensor demonstrated a wide linear detection range from 10 fM to 10 nM with an ultralow detection limit of 0.77 fM, accompanied with high selectivity, good stability, and excellent reproducibility. The constructed ECL aptasensor also showed promising application for the detection of miRNA-122 in living cancer cells. Thereby, the present work not only provides a new ECL aptasensing strategy for the sensitive detection of miRNA in living cancer cells but also puts forward the advancement of the early diagnosis of tumors.</p> Graphical Abstract <p></p>