The fermentation technology coupling with foam separation was studied to relieve the inhibition of target product nisin during fermentation of Lactococcus lactis subsp.lactis ATCC 11454.Coupled operation conditions were determined by Orthogonal-designing experiments as follows: air velocity 40 mL/min,pH 5.75,and aeration duration 90 min.Under the condition,a minimal nisin inactivity rate(6.1%) was achieved.Based on the coupled experiments,fed-batch fermentation was conducted.The results showed that the total nisin activity(4 813 IU/mL) and production(3.37×106 IU) at the end of fermentation increase by 17.5% and 37.0% compared with those in the control group which were 4 813 IU/mL and 2.46×106 IU,respectively.These provided a promising method for industrial production of nisin.