This paper presents a subwavelength grating based multilayer surface plasmon resonance biosensor (SPRB) which includes a periodic array of subwavelength grating on top of a layer of graphene sheet in the biosensor. The proposed biosensor is named grating-graphene SPRB (GG-SPRB). The aim of the proposed multilayer structure is to improve the sensitivity of the SPRB through monitoring of the biomolecular interactions of DNA hybridization. Significant sensitivity improvement is obtained for the GG-SPRB compared with the conventional SPRB. The result of the numerical investigation of the GG-SPRB is presented and compared with a theoretically developed multilayer matrix formalism, and a good agreement has been observed. In addition, an optimization of the grating dimensions including volume factor, grating depth, grating angle, grating period, and grating geometry (e.g., rectangular, sinusoidal and triangular) is presented. The outcome of the investigation presented in this paper identifies desired functioning conditions corresponding to the best design parameters for the GG-SPRB.