According to global requirements to DME as an alternative environment friendly fuel and also regarding the positive effects of employing multifunctional auto-thermal reactors as novel concept in process intensification, direct DME synthesis was coupled with dehydrogenation of cyclohexane in a thermally coupled heat exchanger reactor composed of two separated sides for exothermic and endothermic reactions in our previous study. DME is conventionally produced by a two-stage process which is called the indirect method of DME production. Recently, a new method called direct DME synthesis, have been introduced and gained much more attention due to its economical superiority compared with the indirect method. In this new process, the methanol production and dehydration one occur simultaneously on the hybrid catalysts in only one reactor and consequently the methanol purification unit can be neglected. In the present work, the aforementioned reactor is optimized applying differential evolution (DE) algorithm as an effective and robust optimization method. The objective of this research is to optimize the operating conditions contributing to maximization of the summation of DME and benzene mole fractions in the reactor outlet streams as desired products. The optimal inlet temperatures of exothermic and endothermic sides are determined within their practical range for prevention of catalyst deactivation by sintering. Utilizing the optimization results, the reactor performance would be improved by decreasing of inlet feed flow rates and rising of the production rates of the desired products. This conducted study results in enormous reduction in the operational costs as well as increase of the net profit of the plant. It should be mentioned that an investigation relevant to environmental aspects and commercial viability of the optimized reactor is necessary in order to commercialize the considered process. (C) 2011 Elsevier B.V. All rights reserved.