Herein, protein (bovine serum albumin, BSA) immobilized gold nanoclusters (AuNCs) were synthesized with high quantum yield (~12%) using a hydrothermal reflux method. A high-resolution transmission electron microscopy analysis revealed that the prepared AuNCs were highly dispersive and uniform, with an average size of 3.3 ± 1.82 nm. The AuNCs have successfully employed for the detection of epinephrine in human serum. As a result, sensitive level epinephrine detection in human serum was achieved, with a limit of detection of 910 pM. Interestingly, the rate of photoinduced polymerization for epinephrine absence and presence of AuNCs was found to be 0.0027, and 0.256 min−1, respectively, which was ~95 times much faster than that of neat polymerization of epinephrine. In addition, significant experimental differences were observed from Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and zeta potential measurements before and after the treatment of AuNCs with epinephrine, which gives convincing support for the proposed working mechanism. The results show that the as-prepared AuNCs are potential ideal candidates and can be effectively used for the bio-sensing, bio-imaging, and diagnosis of diseases that are related to epinephrine, such as Alzheimer's and Parkinson's.