In this paper, a novel membrane-assisted fermentation coupling with foam separation (M-FCFS) technology was developed to separate polymyxin E from its broth immediately. The effects of starting aeration time, membrane, volumetric airflow rate in foam column, and nitrogen source (i.e. peptone, also known as foam stabilizer) on the production of polymyxin E were studied. Under the optimal conditions, the total titer (TT) of polymyxin E reached 1.29 x 10(6) IU, resulting in a 50.4% improvement compared with the uncoupling experiment (8.60 x 10(5) IU). This work combined the advantages of foam separation and membrane filtration, and provided a promising technology for the production of polymyxin E.