In this paper, we numerically and experimentally propose a novel hollow-core microstructured optical fiber (HC-MOF) biosensor for refractive index determination. The sensing mechanism of the proposed sensor is based on photonic bandgap effect and the location of transmission maxima of the fiber, which is strongly depend on the liquid analyte RI filled in the fiber core. The proposed HC-MOF biosensor demonstrates the spectral sensitivity of 5636.3 nm/RIU with a RI detection range of 1.333 to 1.3385 for different ratios of plasma in blood serum in our experimental studies. The HC-MOF proposed here can detect similar liquid analytes with RI close to 1.33. The proposed sensor with a high sensitivity, ease of operation and the possibility of real-time sensing has a strong potential for detection of liquid analytes and biomolecules with possible applications in medicine, chemistry, and biology.