Wetting behavior of a droplet on a solid surface has not been fully understood from the macroscopic level to the microscopic level. In order to try to solve this problem, this work adopted a combination of macroscopic force measurement and molecular dynamics simulation to study the wetting interaction between water droplets and kaolinite surface. On the one hand, a macroscopic force measurement system was used to measure directly the wetting force between the millimeter-scale water droplet and the kaolinite substrate. Results showed that the wetting force was of independence on the impact velocity, but mainly dependent on the impact distance, and increased significantly with increasing impact distance due to the enlargement of three-phase contact (TPC) line length. On the other hand, molecular dynamics simulation method based on classical mechanics theory was applied to study the wetting behavior of nanometer-scale water droplets on the (001) surface of kaolinite. Simulation suggested that the overall wettability of the kaolinite surface was determined by the wettability of kaolinite (Al-OH) surface and kaolinite (Si-O) surface. Because the water nanodroplet formed an incomplete monomolecular water layer on the (Al-OH) surface, while the water molecules stayed together as a compact entity keeping a form of deformed sphere on the (Si-O) surface. These findings can provide guidance for the study of droplet-solid interaction mechanism and the explanation of some special wetting phenomena caused by anisotropic surface characteristics.