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For the flow interaction between the podded engine and the airframe of blended wing body configuration(BWB), taking the 300 seats class BWB civil transport NPU-BWB-300 designed by Northwestern Polytechnical University as the research object, the influence of the podded engines on the BWB airframe at typical high and low speed conditions were investigated by CFD method, and the airframe-nacelle interference mechanism was revealed. The results indicate that the podded engines mainly affect the high speed performance of BWB, but have little effect on the low speed performance. The flow interaction between the airframe and the nacelle at high speed condition is serious when podded the engines, which leads to strong shock wave and flow separation. The flow mechanism of the above-mentioned interaction is as follows: firstly, the large supersonic region and shock wave on the nacelle external surface interferes with airframe surface flow seriously, which induces shock wave and flow separation; secondly, a convergent-divergent channel is formed between the airframe and the nacelle, resulting in the "throat" effect, which produces shock wave and flow separation.