The interaction of hydrophobic modifiers with clay mineral surfaces plays an important role in the hydrophobic aggregation sedimentation for the treatment of clay-rich tailing. The adsorption of dodecylamine and oleic acid on kaolinite was investigated at the atomic level by using density functional theory (DFT) calculation and compared with the experimental results of hydrophobic aggregation. The effect of molecular and ionic forms of modifiers as well as the (001) and (00-1) surfaces of kaolinite were examined. The polar head groups of dodecylamine and oleic acid are adsorbed on the kaolinite surface mainly by hydrogen bonding and electrostatic attraction. The ionic and molecular forms are the preferred adsorption species of dodecylamine and oleic acid, respectively. The adsorption ability of kaolinite (001) surface toward dodecylamine and oleic acid is stronger than that of (00-1) surface. The adsorption energies of the complete oleic acid on kaolinite (00-1) surface are positive. In a large pH range, dodecylamine is the preferred hydrophobic modifier of kaolinite relative to oleic acid.