Abstract: Shale contains a lot of clay minerals. Clay minerals mainly exist in nano- and micro-meter sized particles, and the pore structure is complex, which leads to its extremely complex wettability. The surface wettability of clay minerals significantly affects the oil and gas-bearing capacity of shale reservoirs. Therefore, studying the wettability of common clay minerals in shale at the nanoscale is of great significance for shale hydrocarbon exploration and development. In this study, the wetting behavior of water in n-hexane and toluene on different clay mineral surfaces at the nanoscale was systematically studied using Molecular dynamics (MD) simulation. And the influencing factors of wettability were analyzed. Through the analysis of the morphological changes of water, relative concentration of water, RDF and interaction energy, it is concluded that the following order of water wettability on the surfaces of clay minerals: montmorillonite > chlorite > kaolinite > illite. Through the analysis of interaction energy, it is concluded that the hydrophilicity of four clay minerals is stronger than that of lipophilicity. And the main interactions between water and oil and the mineral surfaces were van der Waals force and electrostatic force. In addition, the temperature, liquid hydrocarbon type, and mineralization of water affected the wettability of clay minerals. The concentration of water on the surfaces of montmorillonite, kaolinite, and illite decreased with increasing temperature, and the water wettability decreased. At 298 K, the hydrophilicity of the surfaces of the clay minerals in toluene follows the order montmorillonite > chlorite > kaolinite > illite. The higher the NaHCO3 concentration in water, the weaker the wettability of the clay mineral surfaces to water. By comparing the previous experimental results with the MD simulation results, similar wetting characteristics were obtained, and the reliability of the simulation results was verified. MD simulation was used to explore the water wetting of the surfaces of four clay minerals in a shale reservoir from the micro level. This makes up for the lack of experimental means for clarifying the flow and production mechanisms of shale oil and gas and effectively improves the evaluation technology of shale.