An anti-endotoxin polypeptide is provided. The anti-endotoxin polypeptide having the formula (I) A1-L-C1, wherein A1 and C1 independently is a short peptide with α-helix, L is AGP (Ala-Gly-Pro) or a peptide bond, and the hydrophobicity of the hydrophobic terminus in the anti-endotoxin polypeptide is between about 0.425 and 0.765. The anti-endotoxin polypeptide of the invention can neutralize the lipopolysaccharide and has the low hemolysis and high salt resistance, simultaneously. The present invention also provides a method for design an anti-endotoxin polypeptide, the anti-endotoxic activity is adjusted through increasing and/or decreasing hydrophobicity of the hydrophobic terminal end.
