In this study, we synthesized DFNS with 4 nm pore size (DFNS-4), DFNS with 20 nm pore size (DFNS-20), and smooth nanosilica (SNS). The nanosilica was functionalized with a thin layer of PDA in order to bind and quench fluorophore-labelled short ssDNA. A 6-carboxyfluorescein-labeled single strand oligodeoxynucleotide (FAM-ssDNA) was designed to recognize the target sequence and act as a fluorescent reporter. The FAM-ssDNA and DFNS@DA are combined to form a fluorogenic complex that can be "turned-on" by exposure to the targeted nucleic acid sequences. As shown in Scheme 1, when the FAM-ssDNA is adsorbed on the DFNS@DA surface, the fluorescence is quenched and the FAM-ssDNA/DFNS@DA system is in the "off" state. In the presence of a complementary target sequence, the FAM-ssDNA hybridizes with the target and detaches from the DFNS@DA, leading to recovery of the fluorescence emission. The target sequence therefore acts as a trigger to "turn-on" the FAM-ssDNA/DFNS@DA biosensor. One unique character of the proposed analytical system is the well-defined pore structure of the DFNS. Because of the small pore size, only the FAM-ssDNA can effectively enter the DFNS@DA to serve as fluorescent sensor. For the first proof of concept, we demonstrate the detection of microRNA (miR-21) in living cells using the proposed analytical system. Scheme 1. Schematic illustration of the "turn-on" fluorescence sensing platform for nucleic acid detection. The DFNS@DA adsorbs the labelled ssDNA probe and quench the fluorescence. Hybridization with complementary DNA sequence (cDNA) or microRNA (miR-21) causes the probe to detach from the DFNS@DA to emit fluorescence.