We demonstrate a temperature-insensitive and high-sensitive label-free biosensor for low-concentration Human IgG detection based on S-tapered optical fiber (STF). The sensor is sensitive to local refractive index changes and has high robustness against temperature noise without a temperature control system. The temperature sensitivity of the sensor is −0.02nm/ • C in the range of 25 • C-45 • C. Within 15 minutes at room temperature, the average drift of the center wavelength is 0.04 nm. The calibration experiments demonstrate that STFs for liquid achieved a sensing precision of 0.04 nm and a sensitivity of 538.62 nm/RIU. The STFs are applied for the concentration measurement of multiple diluted ex vivo IgG biomolecule solutions. The results showed that STFs were reliable for low-concentration IgG detection and its lower limit of measurement was demonstrated as 28 ng/ml. With the advantages of temperatureinsensitive, compact size, low cost, high precision, real-time detection, fast response, good specificity, this STF sensors are promising for the antigen detection applications.INDEX TERMS Human IgG, high precision, S-tapered fiber biosensor, temperature-insensitive.