Measurement of interleukin-10 (IL-10) has subsequently become a crucial tool to identify end-stage heart failure (ESHF) patients prone to adverse outcomes during the early phase of left ventricular assisted device (LVAD) implantation. In this context, label-free detection using a novel substrate based on hafnium oxide (HfO 2 ) grown by atomic layer deposition (ALD) on silicon was applied. Here, we studied the interaction between recombinant human (rh) IL-10 with the corresponding monoclonal antibody (mAb) for early cytokine detection of an anti-inflammatory response due to LVAD implantation. For this purpose, HfO 2 has been functionalized using an aldehyde–silane ((11-(triethoxysilyl) undecanal (TESUD)) self-assembled monolayer (SAMs), to directly immobilize the anti-human IL-10 mAb by covalent bonding. The interaction between the antibody–antigen (Ab–Ag) was characterized by fluorescence patterning and electrochemical impedance spectroscopy (EIS). Confirmation for the bio-recognition of the protein was achieved by fluorescence patterning, while Nyquist plots have shown a stepwise variation due to the polarization resistance (R p ) between the Ab activated surfaces with the detection of the protein. For early expression monitoring, commercial proteins of rh IL-10 were analyzed between 0.1pg/mL and 50ng/mL. Protein concentrations within the linear range of 0.1–20pg/mL were detected, and these values formulated a sensitivity of 0.49(ng/mL) −1 . These preliminary results demonstrated that the developed biosensor was sensitive to the detection of rh IL-10, and the measured limit of 0.1pg/mL in phosphate buffered saline (PBS) was clearly detectable, which displays the high sensitivity of EIS. On analysis of an interference attributable to non-specific binding of other cytokine biomarkers; tumor necrosis factor-α (TNF-α) and IL-1β were analyzed without causing an interference to the IL-10 mAb. This established that selective sensitivity was responsive only to rh IL-10. To our knowledge, this is the first biosensor that has been based on HfO 2 for Ag detection by EIS. In time, the HfO 2 insulator will be incorporated into the gate of silicon-based ion-sensitive field-effect transistors (ISFETs) and developed as a portable real time detection system for the IL family of biomarkers in human serum.