Optical fiber based SPR sensors have attracted more and more attention due to their unique advantages over the prism-based SPR sensors. A novel fiber-optic SPR sensor with multi-alternating metal layers for biochemical analysis is presented in this paper. Based on the fundamental SPR theory of the fiber optic sensing technology, we theoretically investigated the effects of the existence of alternating layers deposited on sensing region SPR wavelength changes. The emphasis was placed on the numerical simulation of the fiber-optic SPR sensor’s sensitivity which could be affected by its technical parameters such as the metal thickness, number of alternating layers. Results showed that, compared to the normal SPR sensor with the single metal layer, the proposed sensor had a wider detecting range of the refractive index and higher sensitivity, which can find applications in biological analysis.