Herein, a novel zinc-organic gel with self-catalysis-enhanced electrochemiluminescence (ECL) performance was prepared as an emitter for the first time to assemble a biosensor for ultrasensitive detection of microRNA-221 (miR-221) related to liver cancer. Interestingly, Zn2+ served as a central ion to coordinate with multidentate ligands 2,4,6-tris(4-carboxyphenyl)-1,3,5-triazine (TATB) at room temperature to form Zn-TATB-MOGs with excellent ECL intensity. More importantly, compared to metal ions (e.g., Al3+, Fe3+, and Eu3+) in the reported MOGs with the role of central ions, Zn2+ in Zn-TATB-MOGs not only served as the central ion but also as a coreaction promoter to facilitate the transformation of S2O82- into free radicals SO4•- to react with Zn-TATB-MOGs•- for further enhancing the ECL signal of Zn-TATB-MOGs. This was the first time to explore the promotion function of metal ions for coreaction reagents and realize the self-catalysis-enhanced ECL of MOGs. Additionally, the double domino-like cascade strand displacement amplification (DC-SDA) methods could overcome the shortcomings of time-consuming procedures and low DNA utilization in traditional cascade-free amplification methods, which significantly shortened the response time of the biosensor and improved the utilization rate of DNA. Consequently, the constructed biosensor achieved ultrasensitive detection of miR-221 with a detection limit of 2.19 aM, which was lower than reported works. This work provided new insight into broadening the development and improving the performance of MOGs as emitters, holding promise for applications in trace detection of biomarkers and early disease diagnosis.