Abstract: The flotation process achieves separation between different minerals by altering the hydrophilic/hydrophobic properties of mineral surfaces through the addition of chemical reagents. Simultaneously, water molecules in the flotation system adsorb onto mineral surfaces, thereby influencing surface wettability and modifying the hydrophilic/hydrophobic characteristics. Therefore, studying the surface properties of molybdenite and the interaction between molybdenite surfaces and water molecules is of guiding significance for revealing the microscopic flotation mechanism of molybdenite and selecting suitable flotation reagents. The surface structures and properties of the (001) and (100) surface of molybdenite were studied by dispersion−correction density functional theory (DFT−D) plane−wave pseudopotential method. Comparative analyses were conducted on surface energy, surface relaxation, and density of states (DOS) between different crystal planes. The adsorption configurations of water molecules on surfaces were investigated, and the adsorption energies of water molecules at different sites were calculated. The results demonstrate that the (001) surface exhibits an extremely low surface energy (~0.012 J/m²), while the (100) surface shows approximately 10−fold higher surface energy, indicating greater surface reactivity. The results also indicates that the (001) plane of molybdenite is more stable than the (100) plane, leading to a preferential cleavage parallel to the (001) plane. The calculation of the density of states (DOS) of surface atoms also revealed that Mo and S atoms on the (100) surface have higher electron DOS at the Fermi level, suggesting that the surface atoms on the (100) surface are more active than those on the (001) surface. There is a certain degree of relaxation for the Mo atoms in the first layer and the S atoms in the second layer on the (100) surface, whereas no surface relaxation occurs on the (001) surface. The adsorption of water molecules on the (001) surface is very weak, mainly due to the weak interaction between H in water molecules and S on the surface. In contrast, the adsorption energy at molybdenum (Mo) sites on the (100) surface reaches −94.16 kJ/mol. These results demonstrate that the (001) surface exhibits excellent hydrophobicity, while the (100) surface displays moderate hydrophilicity. This distinction further implies that non−polar collectors preferentially interact with the molybdenite (001) surface, whereas polar collectors exhibit higher affinity towards the (100) surface.