A high sensitivity human chorionic gonadotropin (hCG) detection was conducted by a tapered side-polished (TSP) optical fiber sensor. Experimentally, the TSP fiber sensor was made by side polishing a short section of single mode fiber to a D shape structure and tapering the D shape section to a small diameter (<10 μm in the experiments). By functionalizing the primary antibody of hCG onto the TSP fiber surface, the sensor was used for detecting hCG concentration. Experimental results show that when the hCG concentration is 0.1 mIU/mL, the sensor has an average wavelength shift of 0.82 nm. The limit of detection (LoD) of the hCG is estimated 0.058 mIU/mL, assuming three times of maximum wavelength variation (3×0.15=0.45 nm) in Phosphate buffer saline (PBS) to the measurement limit. The specificity has also been tested by immersing the sensor into a mixed biomaterial solution (hCG -1 mIU/mL, pig-IgG -1 /mL, Staphylococcus aureus -6×105 CFU/mL and Escherichia coli -2.5×105 CFU/mL). The result showed that the TSP optical fiber sensor has excellent specificity. The biosensor has potential application in clinical/medical diagnostics, human health, environmental quality and food safety monitoring.