AbstractInnovative techniques to visualize native microRNAs (miRNAs) in live cells can dramatically impact current research on the roles of miRNA in biology and medicine. Here, we report a novel approach for live‐cell miRNA imaging using a biodegradable MnO₂ nanosheet‐mediated DD‐A FRET hybridization chain reaction (HCR). The MnO₂ nanosheets can adsorb DNA hairpin probes and deliver them into live cells. After entering cells, the MnO₂ nanosheets are degraded by cellular GSH. Then, the target miR‐21 triggers cascaded assembly of the liberated hairpin probes into long dsDNA polymers, which brings each two FAMs (donor) and one TAMRA (acceptor) into close proximity to generate significantly enhanced DD‐A FRET signals, which was discovered and proven by our previous report. We think the developed approach can serve as an excellent intracellular miRNAs detection tool, which promises the potential for biological and disease studies.