<p>Proteins play a crucial role in tissue formation and repair, making their accurate detection essential for biomedical applications. This study presents a square-core photonic crystal fiber sensor (SCPCFS) designed for the sensitive detection of protein concentrations in aqueous solutions. Zeonex is selected as the background material due to its superior optical characteristics in the terahertz (THz) frequency range. Operating within the 0.8–2.2 THz band, the sensor achieves high relative sensitivity at 1.6 THz, with values of 97.667%, 98.33%, 98.781%, 99.072%, and 99.242% corresponding to protein concentrations of 15%, 30%, 45%, 60%, and 75%, respectively. The associated confinement loss values are notably low—4.56, 9.89, 2.26, 5.87, and 2.25 cm⁻¹—indicating minimal signal attenuation. Furthermore, the SCPCFS demonstrates excellent performance across other key optical metrics. Its simple geometric structure facilitates fabrication using current technologies. These features highlight the sensor’s potential for reliable, real-time, and highly sensitive protein concentration monitoring in biomedical and biochemical applications.</p>