The invention discloses a high-sensitivity surface plasma resonance sensor, which consists of a multi-layer medium layer, a transparent dielectric medium substrate (2) and a metal film layer (5), wherein the multi-layer medium layer is alternatively formed by a low-refractive-index medium thin layer (3) and a high-refractive-index medium thin layer (4), one side of the transparent dielectric medium substrate of the sensor is adjacent to a coupling prism (1), one side of the metal film layer is adjacent to a sample (6) to be tested, the total quantity of the low-refractive-index medium thin layer and the high-refractive-index medium thin layer in the multi-layer medium layer is of an odd number, the thickness of each layer is different from each other, and the low-refractive-index medium thin layer in the multi-layer medium layer is always adjacent to both the transparent dielectric medium substrate and the metal film layer. Compared with the traditional surface plasma resonance sensorbased on the single metal film layer, the sensitivity of the sensor is remarkably improved, at the same time the structure of the multi-layer medium layer is relatively simple, total thickness is smaller, the processing is easy, the cost is reduced, and stronger practical value can be realized.