An optical waveguide SPR sensor is adapted for differential measurement. The optical waveguide SPR sensor includes a base, a bottom layer, and at least one set of optical waveguide layers. The set of the optical waveguide layers includes a measuring optical waveguide channel and a reference optical waveguide channel. The measuring optical waveguide channel includes an SPR sensing film layer. The measuring optical waveguide channel and the reference optical waveguide channel are independently configured and substantially parallel one to another. The bottom layer has a refractive index higher than a refractive index of the optical waveguide layer.