Designing and developing the electrochemical analytical equipment based on biomimetic materials and supramolecular chemistry has gained wide attention in recent years because the incorporation of molecular recognition and nanomaterials can effectively enhance the analytical performance and robustness of electrochemical/bio sensors. Herein, an ultrasensitive and robust sandwich-type electrochemical immunosensor has been fabricated for quantitative determination of squamous cell carcinoma antigen (SCCA), a well-defined biomarker of squamous cell carcinoma in human serum. The water-soluble pillar [S]arene functionalized Pd/MoS2 nanosheets are prepared to immobilize the electroactive thionine molecules through host-guest interaction, and employed as labels to capture detection antibodies for signal amplification. Due to the outstanding electrochemical properties, large specific surface area, and excellent catalytic activity of Thi@WP5-Pd/MoS2 nanocomposites, the robust current response towards the oxidation of thionine are achieved. Besides, the Au nanoparticles decorated TiO2 nanosheets are applied to primary antibodies binding via Au-N bond. Under the optimized conditions, the prepared immunosensor offers a wide linear range from 0.001 to 10 ng mL(-1) with a low detection limt of 0.14 pg mL(-1). The satisfying results of analyzing SCCA in human serum suggest a promising application in the clinical monitoring. (C) 2019 Elsevier Ltd. All rights reserved.