<p>A self-enhancing Cu-TBAPy MOF was synthesized, which serves as both an electrochemiluminescence (ECL) emitter and a dual coreactant accelerator. It was then employed as an ECL probe to construct a highly sensitive ECL immunosensor for the sensitive determination of the lung cancer marker Cyfra 21 − 1. Benefiting from its rigid framework structure and the spatial confinement of the TBAPy ligand imposed by Cu²⁺ coordination, thermal dissipation of the excited-state energy from the ligand is effectively suppressed, resulting in a strong ECL signal that renders this material suitable as a probe for ECL immunosensors. Moreover, the Cu²⁺ sites within the MOF catalyze the reduction of K₂S₂O₈ at the electrode to produce the coreactant SO₄^•‒. Meanwhile, the MOF exhibits peroxidase-like activity, catalyzing the reduction of H₂O₂ to generate hydroxyl radicals (OH^•), which further react with K₂S₂O₈ to yield additional SO₄^•‒. Through the dual promotion mechanism, the ECL signal of the MOF is substantially enhanced. The Cu-TBAPy MOF was employed as a probe, and secondary antibody‑labeled polydopamine nanospheres (PDA NPs) were introduced as signal regulators in a sandwich immunoassay. The ECL quenching was achieved through the dual effects of ECL resonance energy transfer between PDA and the MOF, combined with the scavenging of hydroxyl radicals by PDA. Based on the changes in the ECL signal, an ultrasensitive determination of Cyfra 21 − 1 was realized, with a linear range from 10&#xa0;fg/mL to 10 ng/mL and a detection limit as low as 2.04&#xa0;fg/mL. The sensor has been successfully applied to the determination of Cyfra 21 − 1 in serum samples.</p> Graphical Abstract <p></p>