Abstract A sandwich-type electrochemical immunosensor for detection of carcino embryonie antigen (CEA) was fabricated based on supermolecular labeling strategy. In this work, β-cyclodextrin (β-CD)-based host-guest recognition was used to immobilize capture antibody and label detection antibody. β-CDs functionalized multiwalled carbon nanotube (CDs-MWCNT) was used to immobilize adamantanecarboxylic acid (ADA) functionalized capture antibody onto electrode surface based on host-guest interaction between ADA and β-CD. The detection antibody was first labeled with ferrocenecarboxylic acid (Fc) and then attached to magnetic Fe3O4@SiO2 core-shell nanoparticles based on the inclusion interaction between Fc and β-CD. Fc acts as not only a linker molecule but also electroactive specie. The multiplex labeling of Fc on Fe3O4@SiO2 nanoparticles enabled the signals amplification for CEA after the specific immunoreaction, which was monitored by square wave voltammetry. Under the optimal conditions, the immunosensor displayed a relatively wide linear range from 0.001 ng mL− 1 to 15 ng mL− 1 with a detection limit of 0.33 pg mL− 1 for the detection of CEA. The newly designed immunosensor showed a promising potential application in clinical diagnosis.