<p>In order to address the urgent demand for cervical cancer screening, we have developed an electrochemical immunosensor fabricated to detect novel HPV18 E7 oncoprotein. In this study, preparation of intercalated Ti₃C₂-MXene sheets had been done using an etching method and the MXene sheets were modified with 3-Aminopropyltriethoxysilane (APTES) to allow covalent attachment of immobilized antibody (anti-E7) for label-free ultra-sensitive detection of cancer biomarker. The interaction between antigens and antibodies was investigated utilizing square wave voltammetry (SWV) along with the ferri/ferrocyanide redox couple. Moreover, the sensor reported excellent sensitivity across a broad linear detection range from 10 pg mL^− 1 to 500 pg mL^− 1 with a limit of detection (LoD) of 5.11 pg mL^− 1 under optimized conditions. This work represents the first report of electrochemical immunosensor-based detection of the HPV18 E7 oncoprotein, establishing a new sensing strategy for this clinically significant biomarker. The developed immunosensor was extensively validated in comparison to enzyme-linked immunosorbent Assay (ELISA) for quantification of E7 protein in real serum. The immunosensor demonstrated enhanced selectivity, stability, and reusability, suggesting its potential use for point-of-care (PoC) testing with sufficient cervical cancer detection capabilities.</p> Graphical Abstract <p></p>