Biomarker assay has evolved into an invaluable complementary method for early screening and treatment diagnosis of tumors. Limited by the bulky devices, elaborate procedures, and poor detection accuracy, conventional methods fail to meet the demand for portable, universal, as well as high-precision detection. Herein, an optical fiber lossy mode resonance (LMR) immunoprobe implemented by ITO film as the lossy mode support layer is demonstrated for the detection of prostate-specific antigen (PSA), a biomarker for prostate cancer (PCa). Theoretically, the refractive index sensing performance of the optical fiber LMR was verified by constructing a transmission matrix model, providing theoretical guidance for the application of optical fiber LMR sensors. The construction of the PSA immunoprobe was experimentally achieved by functionalizing the optical fiber LMR sensor. The relationship between wavelength shift and PSA concentration was quantified by resonance wavelength interrogation, and the detection limit (LOD) was calculated to be as low as 0.144 ng/mL, making it ideal for early risk management and prognostic diagnosis of PCa. For clinical application, multiple serum samples were analyzed by the optical fiber LMR immunoprobe with favorable precision. Taken together, this work demonstrates considerable promise in applications of label-free, low-cost, compact-size, and convenient early screening for suspected PCa.