MicroRNA 21 (miRNA-21) is reported to be closely associated with the development of heart failure, cardiac fibrosis and hypertrophy, which could be a promising biomarker for the early-diagnosis of heart failure. Herein, we propose a novel colorimetric miRNA detection method through the integration of duplex-specific nuclease (DSN)-based signal amplification and AuNPs assembly induced colorimetry. Highlights of the proposed method are calculated as: (i) no high temperature hybridization process is required; (ii) DSN enzyme induced recycling provides a favorable detection sensitivity and discrimination of color changes. We believe that the proposed DSN enzyme based colorimetric assay can be applied to heart failure related diagnostics.