Waterflooding is an important functional process for low-permeability reservoir development. However, production practice shows that water breakthrough and floods along natural fractures are ubiquitous in low-permeability reservoirs. Therefore, controlling the water injection pressure to prevent water breakthrough and floods along natural fractures is an effective measure for improving the waterflooding development effect. In this paper, an approach is proposed for determining the water injection pressure based on the opening pressure of natural fractures in fractured low-permeability reservoirs. The opening pressures of natural fractures calculated by the analytical method in the paper and the formation-parting pressures are compared based on the production performance in two different fault blocks F16 and Z3 of the Zhouqingzhuang Oilfield in the Bohai Bay Basin, China. The results show that the calculated opening pressures of the natural fractures in fault blocks F16 and Z3 are 31.4 and 42.9 MPa, respectively, and they are close to the opening pressures of natural fractures obtained from the step-rate tests in injection wells (28.6 and 41.1 MPa); whereas, the formation-parting pressures (44.5 and 47.6 MPa) are greater than the opening pressures of natural fractures. This suggests that the opening pressures of natural fractures can be used, instead of the formation-parting pressure, for the maximum threshold of the water injection pressure. Its effectiveness has been confirmed via comparison to the production performances of the other two wells in the Zhouqingzhuang Oilfield and several fractured low-permeability reservoirs in the Ordos Basin, China. This study will have beneficial applications in the design of waterflooding development in low-permeability reservoirs characterized by the presence of natural fractures.