In this study, a novel surface plasmon-coupled electrochemiluminescence (SPC-ECL) biosensor was developed based on bismuth nano-nest and Ti 3 CN quantum dots (Ti 3 CN QDs). First, MXene derivative QDs (Ti 3 CN QDs) with excellent luminescence performance were prepared as the ECL luminescent. The N doping in Ti 3 CN QDs can effectively improve the luminescence performance and catalytic activity. Therefore, the luminescence performance of QDs has been effectively improved. Furthermore, the bismuth nano-nest structure with a strong localized surface plasmon resonance effect has been designed as the sensing interface via the electrochemical deposition method. It was worth noticed that the morphology of bismuth nanomaterials can be controlled effectively on the electrode surface by the step potential method. Due to the abundant surface plasmon hot spots generated between the bismuth nano-nests, the isotropic ECL signal of Ti 3 CN QDs can be not only significantly enhanced by 5.8 times but also converted into polarized emission. Finally, the bismuth nano-nest/Ti 3 CN QD-based SPC-ECL sensor was used to quantify miRNA-421 in the range of 1 fM to 10 nM. The biosensor has been successfully used for miRNA in ascites samples from gastric cancer patients, which indicated that the SPC-ECL sensor developed in this study has great potential for clinical analysis.