Despite the promising application prospects exhibited by entropy-driven catalysis (EDC) DNA nanodevice-founded fluorescence biosensors for imaging disease biomarkers in living bio-samples, they still face challenges of inadequate sensitivity and uncontrollable initiation. In response, we devise a self-propelled DNAzyme-mediated cascading EDC DNA nanodevice initiated by near-infrared light. Firstly, the wide-ranging interface of MnO2 nanosheets is utilized to co-load all essential nucleic acid components required for EDC through physisorption. Following reduction by the prevalent existence of glutathione in biological media, the resultant Mn2+ serves as the self-propelling force for a Mn2+-reliant DNAzyme, which further combines with EDC to carry out a cascading dual-cycle signal amplification. Subsequently, the analyte binding unit is locked by inserting one DNA modulation with a photon-triggered cleavage connector, thereby implementing an upconverting luminescence-enabled NIR light initiation concept to prevent the biosensor from being prematurely activated during bio-delivery. Upon opting for a non-coding microRNA (miRNA-21, commonly overexpressed in diverse cancers) as the model low-abundance analyte, our newly-developed DNA nanodevice showcases ultra-high sensitivity and satisfactory specificity in detection performance. Looking ahead, this biosensing system can function as a high-efficiency imaging toolbox for analyte analysis in living cells and even mouse bodies, making a considerable contribution to employing DNA nanodevices for disease diagnosis.