Accurate evaluation of the tumor-related mRNA expression levels provides important information for cancer diagnosis and therapy. We recently reported a fluorogenic sensor by coupling tetrazine-mediated bioorthogonal reaction with catalytic hairpin assembly for precise imaging of GalNac-T mRNA in live cells. Fluorescence signals are specifically generated by target mRNA triggered spatial localization of bioorthogonal chemicals. The proposed fluorogenic sensor exhibits low detection limit with signal amplification process. Importantly, the method can avoid false-positive results in biological environment because of the “click to release” feature of bioorthogonal reaction. Our method may provide a useful tool for precise imaging of intracellular mRNA with low expression levels.