Reducing background signal is an effective method to improve the sensitivity of amperometric immunosensors, which are significant in the detection of cancer. Herein, a novel immunosensor probe was synthesised using zeolitic imidazolate framework-hydroquinone-bovine serum albumin (ZIF-8-HQ-BSA). Based on the probe, an "off-on" strategy was applied in the immunosensor to amplify ΔI, the current signal "turn off and on". The ZIF-8-HQ-BSA probe initially showed little current signal since ZIF-8 and BSA exhibit poor conductivity. To amplify the current signal "turn on", the structure of ZIF-8 was broken after treatment with HCl, releasing hydroquinone to be absorbed by the polyaniline hydrogel substrate. Hydroquinone can produce a strong signal and also exhibits strong catalytic ability for HO to further enhance the signal. Following this method, the immunosensing platform was used to detect cytokeratins antigen 21-1 (CYFRA21-1) in human serum and revealed a wide liner range from 0.1 pg mL to 100 ng mL with a low detection limit of 0.65 pg mL (S/N = 3), demonstrating good consistency with an electrochemiluminescence immunoassay. Thus, the amperometric immunosensing platform discussed in this work has high potential for application in healthcare monitoring, clinical diagnostics, and biomedical devices.