Gold nanoparticles functionalized hollow mesoporous Prussian blue nanoparticles (Au@HMPB NPs) were synthesized and its peroxidase-like activity was explored for electrochemical probe. The Au@HMPB NPs can reduce H2O2 at low detection potential of-0.1 V with high sensitivity. After physically adsorption of antibodies onto the gold nanoparticle surface, the functionalized nanoparticles were ted into immuno-probe. The solubleα-chain of interleukin-2 (IL-2) receptor (sCD25) was chosen as a model protein biomarker to test the performance of the probe. sCD25 in the samples were captured and enriched by capture anti-CD25 antibody functionalized magnetic nanospheres. Detection antibody functionalizedAu@HMPBcanthen belinkedontothenanospheresandgenerateelectrochemicalcurrent towards H2O2 reduction. The electrochemical responses to 1 mmol/L H2O2 was increased with the increasing concentration of CD25.