In the design of multistream plate-fin heat exchangers (MPFHEs), surface selection and layer pattern optimization have been investigated as two independent problems and still remain at the empirical stage, which becomes an obstacle for optimizing the performance of MPFHEs. A combined method of the equipartition of entropy production and the balance of local heat load is proposed in the present research to consider these two problems simultaneously, by means of which the decrease of heat transfer performance and the increase of pressure drop caused by inappropriate surface selection and layer pattern could be reduced to a large extent. The temperature difference and pressure drop are introduced into the optimization model in the forms of specific entropy generation rates of the heat transfer and fluid friction. These parameters are adopted as a dual-objective function in the optimization to associate the surface selection with the layer pattern. This combined method starts from the design of layer numbers and fin structures, includes the layer pattern arrangement and finally employs multi-objective optimization to achieve an optimal production. This method conforms to the actual design process and provides good robustness and high efficiency for a main heat exchanger in air separation plants, which is a beneficial approach for the design of MPFHEs. (C) 2016 Elsevier Ltd. All rights reserved.