Polyethyleneimine (PEI) is known for its antibacterial properties and ease of modification. How to improve the specific antibacterial activity of PEI with low toxicity is a research hotspot. In this work, the PEI was used to synthesize a fucose-modified polyethyleneimine copolymer particles (Fuc-PEI CPs) via nucleophilic addition between primary amine and aldehyde groups. Fucose (Fuc) can capture Pseudomonas aeruginosa (P. aeruginosa) with LecB, which has a good targeting property toward P. aeruginosa. The Fuc-PEI CPs' antibacterial activity was investigated by plate counting method. Compared with unmodified PEI, Fuc-PEI CPs (2.5 mu g/mL) showed unique bactericidal ability against P. aeruginosa, and less cytotoxicity and excellent biocompatibility. The antimicrobial mechanism indicated that the improvement of PEI antibacterial activity against P. aeruginosa ascribed to the Fuc's unique recognition of bacteria and PEIs' ability to destroy the cell membrane of bacteria. The Fuc-PEI CPs as a new antibacterial agent shed light on the constructing a novel antibacterial pathway for killing P. aeruginosa.