There is urgent need for effective bactericidal agents for use in real commercial formulations since many old disinfectants, such as halogenated compounds, are now banned. Cationic polymers may have good bactericidal properties in pure water or buffer, but typically become ineffective in the presence of anionic surfactants that are widely used in many commercial formulations. Here, we discover that polyion complex (PIC) nanoparticles formed by cationic polymers of Poly(3-AcrylaMidoPropyl) TriMethylAmmonium chloride (PAMPTMA) in the presence of anionic surfactants display promising fast-bactericidal effect (> 99.99 % killing within 10-min treatment) on Gram-negative Escherichia coli (E. coli, ATCC ® 8739™). To examine the influence of hydrophobicity on bactericidal property, we synthesize PAMPTMA-b-Poly(Butyl MethAcrylate) and discover that increasing hydrophobicity has little influence on bactericidal property of PIC nanoparticles. Mechanism study shows that cationic PIC nanoparticles rapidly cause significant pores both in the outer-and inner-membranes because of their large size and high local concentration of positive charges. The rapid membrane pore formation results in fast cell death. The discovery --certain cationic polymers when formulated with anionic surfactants are even more bactericidal than neat cationic polymers alone --paves the way for potential applications of synthetic cationic polymers in commercial formulations.