Abstract: To explore the antimicrobial activity of epidermis mucus, the basic components and amino acid composition were analyzed and the antimicrobial substances in the mucus were extracted in this study. Their antimicrobial activity, preservation effects on salmon were explored. The components with antimicrobial activity were isolated and purified by solid phase extraction, gel filtration chromatography and reverse phase high performance liquid chromatography. And the peptide sequences were identified. Then, the antimicrobial peptides were synthesized accordingly and their antimicrobial activities were verified. The results exhibited that the main composition of epidermis mucus of sturgeon was protein with 47.44%±0.59%. The total amino acid content was 459.68 mg/g, with a high content of basic amino acids and hydrophobic amino acids. The crude antimicrobial peptide exhibited significant antimicrobial activity against Bacillus subtilis. Crude antimicrobial peptide (50 mg/mL) significantly inhibited the growth of microorganisms and protein degradation during salmon preservation. The highest active component after final liquid chromatography purification exhibited an inhibition rate of 92.40%±4.50% against Bacillus subtilis and 75.43%±5.02% against Escherichia coli. The sequences of novel peptides were identified as HSETLHDV and PLTDWQL. The synthetic antimicrobial peptides of sturgeon epidermis mucus had obvious inhibitory effects on Bacillus subtilis, Escherichia coli and Shewanella baltica. Therefore, this study would provide a theoretical basis for exploring the antimicrobial value of sturgeon mucus and lay a foundation for the development and application of natural preservatives.