In this article, the plantwide control of a novel process for diethyl oxalate production via two steps is investigated. The unique feature of this process is that there is a closed regeneration-coupling circulation. It results in that two steps should be matched properly and mass balance for overall reaction should be satisfied precisely. An effective control structure using a feedforward ratio with composition controller is determined. Later, safety analysis for this process is investigated by the integration of dynamic simulation and HAZOP (hazard and operability analysis). In comparison with heuristic HAZOP, quantitative deviations can be introduced. Quantitative variation trends and change rates of important variables can be determined. Determining increase rate in temperature and pressure is significantly important, since response time as indirect indictor can be used to assess the possibility of risk. Finally, a general procedure based on simulation for design and safety analysis of chemical process is proposed. (C) 2018 Elsevier Ltd. All rights reserved.