The layout of chemical plants is a significant step to promote the safe and efficient operation of a chemical factory. In the actual production process, the chemical process plant layout may be affected by immovable hazards outside the available layout area. In this paper, the external hazard unit is arranged as one of the chemical process plants. The domino effect potential of all chemical process plants is quantified by using the classical domino hazard index (DHI). A layout optimization model considering the effects of external hazard units has been proposed to obtain the optimal plant layout from economic and safety aspects. The feasible layout solutions are obtained under the orientation, boundary and non-overlapping constraints by the non-dominated sorting genetic algorithm II (NSGA-Ⅱ). The proposed model is further analyzed through a hypothetical case of three storage tanks outside the acrylic acid (AA) production plant layout area. The results show that the total cost range for the optimal solution is 650348–1365443 $, with corresponding DHI values ranging from 29 to 129. The plant with larger DHI value will be arranged to far away from the external hazard units to obtain a safer layout. This work can provide rational layout solutions for the layout designers to make different decisions according to the actual situation.