<p> A novel electrochemiluminescence (ECL) immunosensor based on the resonance energy transfer (RET) effect between europium-based metal-organic framework (Eu-MOF, ETM) and GO-PEI/Au was developed for detecting neuron-specific enolase&#xa0;(NSE). First, using 4’,5’-Bis(4-carboxyphenyl)-[1,1’:2’,1”-terphenyl]-4,4”-dicarboxylic acid (TCPB) as the ligand, we synthesized an efficient and stable ECL emitter (ETM) as the signaling substrate. Due to efficient spectral overlap between the ECL emission spectrum of ETM and the UV-vis absorption spectrum of GO-PEI/Au, the ECL emission signal of ETM can be expeditiously quenched. Consequently, the ECL varied with the quenching efficiency of the immunosensor, which correlated with the target analyte concentration, enabling quantitative detection of NSE. The developed straightforward and cost-effective immunosensor exhibited outstanding sensitivity and selectivity in identifying NSE within the 10&#xa0;fg mL^− 1 to 100 ng mL^− 1 range with an impressively low limit of detection (LOD) of 1.26&#xa0;fg mL^− 1. The immunosensor was successfully applied to quantify NSE in clinical human serum samples. Furthermore, by substituting the quenching probe, this platform can be readily adapted for detecting diverse biomarkers, demonstrating significant potential utility. To sum up, based on the ECL-RET strategy, a highly sensitive ECL immunosensor for NSE detection was constructed. It incorporated a novel ECL emitter (ETM) and established a new energy donor-acceptor pair, which demonstrated effective preliminary analysis of clinical samples.</p> Graphical Abstract <p></p>