In this study, a bilevel programming model is proposed for a multiple decision-subject location-routing problem of hazardous waste (HW) under a fuzzy random environment to select the best HW disposal centers. In this proposed model, the objective of the upper level decision makers is to select the best location of HW disposal centers to minimize total costs and risk loss, while the goal of followers is to select an optimal HW disposal center to minimize transportation costs. However, the amount of HW generated is difficult to estimate, so we consider the amount of HW generated as a fuzzy random parameter in this article. Then, we developed a binary particle swarm optimization based on fuzzy random simulation (FRS) to address the proposed model, and a case study was applied to verify the effectiveness and feasibility of the proposed model and algorithm. Therefore, some interesting findings are obtained: (i) the results show that the bilevel programming model is suitable for such problems; (ii) the bilevel programming model proposed herein is flexible, and the parameters can be adjusted to meet different requirements; and (iii) the comparison between binary particle swarm optimization (PSO) based on FRS and classical PSO further illustrates the advantages of the proposed algorithm. Moreover, due to the flexibility of the proposed method, the proposed bilevel programming model in this article can be applied to other similar research problems.