An optical differential detection technique for the surface plasmon resonance (SPR) sensing is proposed. In our system, we combine a method of differential detection and SPR technique. The measurement sensitivity of refractive index is about 10-5 RIU (Refractive Index Unit). There are several advantages like immediate detection and high sensitivity in our system. This technique can be applied to the small biological molecule interaction. It is expected to combine the biological molecule on bio-chip array for massive parallel screens.