To address the challenge of highly sensitive and accurate detection of biomarkers in complex environments, a rational engineering strategy for designing electrochemical immunosensing platform is proposed. Herein, we develop a microsensor chip through the combination of multiplexed electrodes and microfluidic channels for the parallel detection of human interleukins (IL-6 and IL-8). For the construction of an efficient sensing interface, the conductive silver nanowires (Ag NWs) wrapped with zeolitic imidazolate framework (ZIF-8) thin film (denoted as ZIF-8@Ag NWs) are prepared, and then employed for the multi-functionalization of electrodes. The immunodetection of ILs is based on the direct signal transduction ability of Ag NWs and specific interaction of periodically arranged Zn²⁺ ions in ZIF-8 films with biomolecules, which offer the high assay sensitivity and good specificity. The immunosensor chip achieves a wide detection range from pg/mL to ng/mL and possesses the ability to resist non-specific proteins adsorption in biological complex media. Further clinical serum samples assay verifies that the combination of IL-6 and IL-8 levels yields high diagnostic accuracy. Principal component analysis (PCA) reveals that 18 patient samples could be fully separated from healthy control samples. The low-cost, easily fabricated electrochemical immunosensing platform provides a rapid serum test for diagnosis and personalized therapy of inflammatory diseases, and can also be generalized to other immunoreaction-based biomarkers detections.