Abstract <p>Over the past few decades, optical sensors based on surface plasmon resonance (SPR) in attenuated total reflection (ATR) configurations have emerged as powerful tools for label-free biochemical sensing. SPR high sensitivity to refractive index variations enables precise monitoring of molecular interactions. Here, we propose a novel SPR-based sensor that employs Weyl semimetal (WSM) to excite low-loss surface plasmon polaritons (SPPs) in the mid-infrared regime, optimized for skin cancer detection. The designed structure supports a sharp Fano resonance (FR) localized at the WSM and sensing medium interface. This FR manifests as an asymmetric lineshape with an ultra-narrow width, significantly enhancing sensitivity to refractive index changes in the analyte. Numerical simulations demonstrate that the SPP mode resonance angle exhibits exceptional sensitivity (<i>S</i> = 113.50°/RIU) and an ultra-high figure of merit (FOM = 22 700 RIU^–1) to the dielectric environment. This performance makes the sensor ideal for detecting subtle biomolecular shifts associated with early-stage skin cancer biomarkers. We also systematically investigate the influence of the WSM layer Fermi energy and node separation length on sensor performance. These parameters critically govern SPP dispersion and loss characteristics, enabling spectral tunability across the mid-IR range.</p>