The grain boundaries of graphene are disordered topological defects, which would strongly affect the physical andchemical properties of graphene. In this paper, the spectral characteristics and photoresponse of MoS2/graphene het-erostructures are studied. It is found that the blueshift of the G and 2D peaks of graphene in Raman spectrum is due to doping. The lattice mismatch at the graphene boundaries results in a blueshift of MoS2 features in the photoluminescence spectra, comparing to the MoS2 grown on SiO2. In addition, the photocurrent signal in MoS2/hexagonal single-crystal graphene heterostructures is successfully captured without bias, but not in MoS2/polycrystalline graphene heterostructures. The electron scattering at graphene grain boundaries affects the optical response of MoS2/graphene heterostructures. The photoresponse of the device is attributed to the optical absorption and response of MoS2 and the high carrier mobility of graphene. These findings offer a new approach to develop optoelectronic devices based on two-dimensional material heterostructures.