<p>Aberrant overexpression of c-Myc protein (c-Myc) serves as a critical biomarker for aggressive lymphomas, yet its trace-level quantification remains challenging due to insufficient sensitivity in conventional assays. Here, we present an electrochemical immunosensor leveraging homogeneous gold–palladium (AuPd) nanohybrids for dual amplification, achieving both simplified fabrication and enhanced analytical performance. A chitosan–graphene oxide–AuPd nanorod composite (CS-GO-AuPd) was engineered as an electrode modifier, offering high conductivity, biocompatibility, and abundant antibody immobilization sites. Prussian blue-doped AuPd nanoparticles (PB-AuPd@Ab₂) were simultaneously designed as catalytic signal probes, synergistically amplifying responses through electron mediation and nanozyme activity. This homogeneous material strategy eliminated heterogeneous nanomaterial interfaces, streamlining sensor assembly while ensuring signal reproducibility. The sandwich-type immunocomplex formation triggered a PB-derived differential pulse voltammetry signal proportional to c-Myc concentration, yielding a 0.5&#xa0;pg&#xa0;mL⁻¹–1&#xa0;ng&#xa0;mL⁻¹ linear range, with a detection limit of 0.25&#xa0;pg&#xa0;mL⁻¹. Comparative validation against clinical methods confirmed robust accuracy, highlighting the platform’s potential for dynamic monitoring of lymphoma progression and therapy response. This work establishes a paradigm for unifying material homogeneity with dual-amplification mechanisms in biosensing, extensible to diverse low-abundance biomarkers.</p> Graphical Abstract <p></p>