Abstract: The flow distribution in vertical and lateral dimensions inside the plate-fin heat exchanger is not uniform, leading to the deterioration of its heat transfer performance. In this paper, a novel structure of plate-fin heat exchanger was constructed by changing the number of inlet and outlet pipes, the inlet and outlet modes and the relative position of the inlet pipe at the end, based on the single-phase flow distribution theory and the flow field characteristics inside plate-fin heat exchanger. Then, the flow distribution characteristics before and after the optimization of plate-fin heat exchanger were numerically simulated by means of the Fluent numerical calculation based on CFD method. Finally, the effecting laws on the flow distribution by the relative position of the inlet pipe, the number of inlet pipes and the number of outlet pipes after the optimization were studied. It is shown that changing inlet and outlet modes can balance the total pressure drop of all paths at inlets and outlets, so as to effectively improve the flow distribution characteristics of plate-fin heat exchanger. In addition, the optimal structure parameter combination of the optimized plate-fin heat exchanger is the relative position of the inlet pipe at the end of 0.033, 5 inlet pipes and 1 outlet pipes, which can decrease the nonuniformity of gas and liquid flow by 50% or so. The research results are of great significance to enhance the heat transfer performance of heat exchangers.