Abstract: To reveal the microscopic mechanism of the influence of Ca²⁺ substitution on the interaction between kaolinite and coal particles, and to address challenges such as the difficult sedimentation of highly argillized coal slurry, dewatering hurdles for fine coal slime, and contamination of flotation clean coal, molecular dynamics (MD) simulations were employed. The adsorption behavior, interfacial interaction energy, and the distribution characteristics of water layers and ions of coal molecules on kaolinite surfaces with varying Ca²⁺ substitution amounts in aqueous environments were calculated. Combined with free settling and flotation tests, the effects of Ca²⁺ substitution levels and solution pH on the dispersion-aggregation states and flotation separation efficiency of the kaolinite-coal particle system were systematically investigated. The results indicate that at low Ca²⁺ substitution levels, the van der Waals and Coulombic interactions between coal molecules and the kaolinite surface are enhanced; the negative charges generated by substitution are adsorbed by the deprotonated functional groups of the coal molecules, leading to particle aggregation and sedimentation, which reduces the turbidity of the supernatant. As the Ca²⁺ substitution amount increases, the electronegativity and interfacial water layer density of the kaolinite surface continue to rise, with counter-ions enriching at the surface. Once the deprotonation of functional groups on the coal molecular surface reaches saturation, the electrostatic and hydration repulsions between kaolinite and coal particles are significantly strengthened, enhancing system dispersion and increasing supernatant turbidity. By altering the electronegativity and hydration characteristics of the kaolinite surface, Ca²⁺ substitution regulates interfacial interactions and enhances the dispersibility of fine kaolinite particles. This makes coal slurry more difficult to clarify and increases dewatering difficulty for fine coal slime. Simultaneously, it weakens the adsorption between kaolinite and coal particles, significantly reducing the contamination of flotation clean coal by kaolinite.