The invention relates to a cyclic lipopeptide derivative and preparation and application thereof. The cyclic lipopeptide derivative is a compound with a structure as shown in a formula A, wherein A1,A2, A3, A4, A5, A6, A7 and A8 are all amino acids, and every two of the A1, A2, A3, A4, A5, A6, A7 and A8 are connected through an amido bond. The A1 is L-Asn; the A2 is L-Tyr or D-Tyr; the A3 is L-Asn or D-Asn; the A4 is L-Ser or D-Ser; the A5 is L-Asn or D-Asn; the A6 is L-Gln; the A7 is L-Pro; and the A8 is L-Cys, and a hydrogen atom on -SH of L-Cys is substituted by one of the following groups: a C1-C18 alkyl group, C4-C11 carboxylic acid, a C4-C11 alkyl cyano group, and a C4-C11 carboxylic acid methyl ester. The cyclic lipopeptide derivative has an excellent antibacterial effect.