To obtain a near optimal solution for operating procedure synthesis under safety constraint, in this paper, we aim at applying a meta-heuristic method termed differential evolution (DE). Compared with the approaches reported previously, we have shown DE's ability to derive such an operating sequence that is adaptive to various practical requirements. Since the algorithm is straightforward and flexible to manage various conditions appearing in real-world applications, we can claim that the proposed approach has great promise. In a case study, we applied the proposed method to safety mixing operation of acrylic acid synthesis process and validated its adaptability under various significant practical conditions.