Bimetallic core−shell nanostructures possess modifiable or tunable localized surface plasmon resonance (LSPR) characters through the alterations of element and configuration. Herein, we described the use of plasmon-tunable Ag@Au bimetallic core−shell nanostructures to improve the electrochemiluminescence (ECL) emission of quantum dots (QDs) for microRNA sensing. Varying the concentration of the initial Ag seed and Au source allowed the size of the Ag core and Au shell to be altered by stepwise galvanic replacement and chemical reduction. The absorption bands of the resultant Ag@Au core−shell nanostructures closely overlapped with the ECL emission spectra of QDs, resulting in an effective LSPR-enhanced ECL emission. Changing the distance between CdS QDs and Ag@Au nanostructures showed that the LSPR-enhanced ECL was distance-dependent. Furthermore, an innovative LSPR-enhanced ECL sensor incorporating a catalytic hairpin assembly-based signal amplification system enabled the sensitive analysis of microRNA-21 (miRNA-21). The linear response range and detection limit were obtained to be 50 aM−10 pM and 20 aM, respectively, and the practical bioassay applications of the sensor were confirmed using HeLa cells and human serums with acceptable results. This pioneering work provided insights into the role of plasmon-tunable Ag@Au bimetallic core−shell nanostructures in enhancing the sensitivity of ECL sensors.