A highly sensitive sandwich-type electrochemical immunosensor was developed for the quantitative detection of breast cancer susceptibility protein 1 (BRCA1), leveraging the synergistic amplification of zeolitic imidazolate framework-8 decorated with gold nanoparticles (AuNPs@ZIF-8) and nitrogen-doped graphene quantum dots (N-GQDs). The AuNPs@ZIF-8 nanocomposite provided a high specific surface area and enhanced electron transfer, enabling dense immobilization of capture antibodies, while N-GQDs acted as signal labels for secondary antibody conjugation. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) confirmed the stepwise assembly of the sensing interface. Differential pulse voltammetry revealed a linear response between 1.0 pg/mL and 50 ng/mL (ΔI (µA) = 3.58 log C + 7.21, R
2
= 0.9985), with a detection limit of 0.3 pg/mL. The immunosensor exhibited excellent selectivity against potential interferents, with non-specific responses below 5%, and demonstrated good reproducibility (RSD = 3.8%) and long-term stability (92.5% signal retention after 30 days). Recovery rates in spiked human serum ranged from 96.8% to 104.2%, confirming the robustness of the platform in complex biological matrices. Compared with conventional methods, the sensor achieved superior sensitivity and operational simplicity. This work highlights a versatile nanocomposite-based amplification strategy for ultrasensitive protein detection and provides a promising analytical tool for clinical screening of breast cancer biomarkers and other disease-related proteins.