Due to the low yield of bacteriocin in lactic acid (LAB) bacteria fermentation， optimizing fermentation conditions of bacteriocin-producing by LAB is the most direct way. Antibiotic resistance tests， hemolysis tests and and whole genome sequence analysis showed that Lactiplantibacillus plantarum NMGL2 isolated from Inner Mongolian cheese did not carry high virulence factors and had no significant virulence effects and had no risk of metastasis of resistance genes， demonstrating the safety of L. plantarum NMGL2 in phenotype and genotype. Then， the fermentation conditions of bacteriocin produced production by L. plantarum NMGL2 were optimized， with Staphylococcus aureus as the indicator bacteria and the diameter of the antimicrobial ring as the investigation target. First， a single-factor test including inoculation rate， initial fermentation pH， culture temperature and liquid medium volume on bacteriocin production was performed. Based on the results of single-factor test， three significant factors including inoculation rate， initial fermentation pH and culture temperature were optimized by the response surface of the three-factor three-level design of the Box-Behnken method. The optimal fermentation conditions for bacteriocin production by L. plantarum NMGL2 were determined and the results showed that the optimal fermentation conditions were initial fermentation pH 7.0， inoculation rate of 1.3%， culture temperature of 37 ℃. The verification test results showed that the inhibition zone diameter of the indicator bacteria (Staphylococcus aureus) was 13.8 mm under the optimized fermentation conditions， which was basically consistent with the predicted value of the model (13.4 mm)， and the fitting rate reached 96.64%， indicating that the model was reliable and effective. This study provide a technical foundation for he production of bacteriocin by Lactobacillus plantarum NMGL2 and its application.