Abstract: In order to verify the feasibility of plasma exosomes as a novel biomarker for the detection of colorectal cancer, a terahertz metamaterial biosensor was designed. The terahertz metamaterial biosensor was designed using a full wave electromagnetic simulation software based on the finite integration time domain method and fabricated by a surface micromachining process. First, the application of the silane coupling agent APTES on the surface of silica improves the adhesion performance of the surface of silica, and Au-Nanoparticles (AuNPs) were used to modify the biosensor surface. Then, by the ligand exchange method, carboxyl groups were introduced on the surface of AuNPs, and the heterobifunctional polyethylene glycol (HS-PEG-COOH) was assembled on the AuNPs. Subsequently, the heat shock protein 60 (HSP60) antibody specific for exosomes was modified. Exosomes were extracted by the instructions of Exosomes Isolation and Purification Kit, and identified by using transmission electron microscope, Western blot, and nanoparticle tracking analysis. The biosensor covered with plasma derived exosomes of colorectal cancer patients showed different resonant frequency shift from that with healthy controls derived exosomes.