A general optimization model is proposed to determine the optimal plant layout with the simultaneous consideration of economic and safety aspects. An important characteristic of the proposed optimization model is that it allows the relocation of some of the existing units to reduce the risks associated with current locations. The formulation also allows the addition of new units. A multiobjective mixed-integer linear programming model (MO-MILP) is developed to determine the optimal location of new and existing units while accounting for cost and risk. The proposed model is analyzed through a case study for a hexane distillation process showing the advantages of considering the possibility of relocating units originally installed following exclusively heuristic approaches and economic criteria.