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This paper proposes a novel method by employing gold-nanoparticle to enhance optic fiber Fabry-Perot (F-P) interferometry signal for bio-molecule detection. PDMS dip coating and self-assembly monolayers were employed to prepare the fiber probes in the formation of F-P cavity and modification of the tip surface, respectively. Cysteine molecules were immobilized on the sensor surface to allow gold-nanoparticles attachment in the experiment. Experiment result shows that the signal amplitude has more than 40% enhancement and the spectrum shift can be improved by one order of magnitude when employing 40 nm nanoparticles compare to the traditional detection ways by Fabry-Perot interferometry. This result provides a minimum detectable gold-nanoparticles concentration of 1 × 107 particles/μl for 40 nm particle diameter enhanced optic fiber Fabry-Perot interferometry.