Results of the studies are reported relating to application of the silanized nanostructured zirconia, electrophoretically deposited onto indium tin oxide (ITO) coated glass for covalent immobilization of the monoclonal antibodies (anti‐CYFRA‐21‐1). This biosensing platform has been utilized for a simple, efficient, noninvasive, and label‐free detection of oral cancer via cyclic voltammetry technique. The results of electrochemical response studies conducted on bovine serum albumin (BSA)/anti‐CYFRA‐21‐1/3‐aminopropyl triethoxy silane (APTES)/ZrO2/ITO immunoelectrode reveal that this immunoelectrode can be used to measure CYFRA‐21‐1 (oral cancer biomarker) concentration in saliva samples, with a high sensitivity of 2.2 mA mL ng−1, a linear detection range of 2–16 ng mL−1, and stability of six weeks. The results of these studies have been validated via enzyme‐linked immunosorbent assay.