Plant layout research contributes to reducing plant construction costs. In general, these problems have been solved by mixed integer non-linear programming (MINLP) models based on objective functions and various constraints. Moreover, many researchers have tried to combine safety issues for reducing expected losses generated by potential accidents in construction costs. However, these combinations of the objective function are very difficult and subjective, since there is no certain definition of the bias parameter that controls the trade-off between construction cost and the expected losses from potential accidents. In addition, in the real engineering industry, safety issues for mitigating potential accidents are considered after the overall plant layout has been determined. Through consider real engineering procedures, this study aims to provide systematic procedures for how to determine the position of plant equipment, and a safety device (blast walls). This problem is designed using two-step optimization approaches. The first step is to investigate the optimal locations of process equipment by considering operational costs and pipeline installation to minimize the construction costs and satisfy various constraints. The second step is to determine the optimal position of blast walls to maximize the mitigation effects of potential explosions. A case study is illustrated to verify that the proposed approach can provide optimal solutions for the locations of plant equipment and blast walls and can be easily applied in other processes. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.