The hydrophobic aggregation of fine particles in high muddied coal slurry water in the presence of four quaternary ammonium salts of 1231(dodecyl trimethyl ammonium chloride), 1431(tetradecyl trimethyl ammonium chloride), 1631(cetyl trimethyl ammonium chloride) and 1831(octadecyl trimethyl ammonium chloride) was investigated through the measurement of contact angles, zeta potentials, aggregation observation, adsorption and sedimentation. The results show that quaternary ammonium salts can enhance the hydrophobicity and reduce the electronegativity of particle surface, and thus induce a strong hydrophobic aggregation of slurry fine particles which promotes the settlement of coal slurry water. The adsorption of quaternary ammonium salts on slurry particles increases with the increase of alkyl chain length and reagent dosage, and will reach equilibrium when the dosage reaches a certain value. Weak alkaline conditions also can promote quaternary ammonium salts to be adsorbed on the coal slurry fine particles. In addition, reasonable energy input and a chemical environment of weak alkaline solution are conducive to hydrophobic aggregation settlement of high muddied coal slurry water with quaternary ammonium salts. The main mechanism of hydrophobic aggregation of coal slurry particles with quaternary ammonium salts is 'adsorption charge neutralization' and hydrophobic interaction.