Interfacial bonding and electronic properties are very important for understanding the photocatalytic activity of heterojunction. However, theoretical research is still lacking in BiPO4(100)/graphene heterojunction. In this study, the photoelectrochemical properties of the BiPO4(100) surface were modified through the introduction of graphene, and the corresponding effect of interface cohesive interaction on the charge redistribution and the band edge of BiPO4(100)/graphene heterojunction was investigated by first-principle calculations incorporating semiempirical dispersion-correction schemes. The results indicated that BiPO4(100) and graphene were in parallel contact and formed a stable van der Waals heterojunction with low lattice mismatch. In addition, it was identified by analyzing the energy band structures and the three-dimensional charge density difference that to couple with graphene, the BiPO4(100) layer in interface took an obvious electron accumulation. It was identified that the hybridization between the two components induces a decrease of band gap and then an increase of optical absorption of BiPO4(100) in visible-light region. Combining the decrease of the band gap of BiPO4 in heterojunction, the potential of the conduction band minimum of BiPO4(100) in heterojunction increased to -1.84 eV, which enhanced its reduction capacity. These results demonstrated that the heterojunction of BiPO4(100)/graphene exhibited higher quantum efficiency under visible-light irradiation. A deep understanding of the microcosmic mechanisms of interface interaction and charge transfer in this system can be helpful for fabricating BiPO4-based heterojunction photocatalysts. Moreover, our work may provide insights for understanding of the mechanism of BiPO4(100)/graphene heterojunctions on photocatalytic activity, which also help in designing other new heterojunction combinations.