Abstract A new immunoprobe based on ferric hydroxide nanocage (Fe(OH)3-NC) was designed to construct an amperometric immunosensor to detect tumour marker. Using the sacrificial template method, the Fe(OH)3-NC was facilely synthesized according to Pearson’s hard and soft acid-base principle. The immunoprobe was fabricated by immobilizing antibodies on reduced graphene oxide-Au composite combined with Fe(OH)3-NC. Fenton-like reaction can be triggered by Fe(OH)3-NC to degrade the methylene blue molecules fixed in the substrate of electrode, resulting in the decrease of current signal which had correlation with the concentration of target analyte. Dissimilar to other Fenton and Fenton-like catalysts with dependence of strong acid or poor molecule-accessibility, the as-prepared Fe(OH)3-NC had more reachable catalytic sites due to its composition and incompact structure. Therefore, the analytical performance of the immunosensor was remarkably enhanced. Under optimal conditions, the immunosensor exhibited an improved performance for CA 19-9, a model analyte, in a wide linear range from 0.00001 to 100 U mL−1 and an ultra-low detection limit of 0.785 μU mL−1. For serum sample, this immunosensor demonstrated excellent consistency with electrochemiluminescence. This work will be of significance in designing new Fenton and Fenton-like catalysts for electrochemical immunosensors.