With Nisin-producing Lactococcus lactis as the starting strain, the strain with tolerance to 10 000 IU/mL Nisin is selected on high-concentration Nisin medium. The Nisin titer of the strain is up to 1 680 IU/mL. As the starting strain, the strain is further treated by atmospheric and room temperature plasmas(ARTP) and mutant strain for high yield of Nisin is quickly selected with 24 well culture plate. At a survival rate of 3%, the positive mutation rate of the Lactococcus lactis is 273% compared with the starting strain. The results of shake flask culture further confirmed that one positive mutant strains could produce 6 120 IU/mL Nisin.