Understanding the wettability of clay mineral surfaces is crucial for enhancing oil recovery, investigating primary migration of hydrocarbon, and evaluating the performance of sealing rocks in a petroleum system. On the basis of molecular dynamics simulations, we investigated the interactions between four typical clay minerals (i.e., pyrophyllite, montmorillonite, illite, and kaolinite) and confined pore fluids (i.e., water/alkane/salts). The influences of surface group, layer charge, and salts on the wettability of clay surfaces were revealed. As the layer charge increases, the hydrophilicity of the montmorillonite basal surface gradually increases. The basal surface of 2:1-type pyrophyllite is completely alkane-wet independent of salts. However, for 1:1-type kaolinite, the presence of salts makes the siloxane surface completely water-wet, whereas it is partially alkane-wet at the absence of salts. In general, the salt ions adsorbed onto clay surfaces promote the surface hydrophilicity. By using nonequilibrium molecular dynamics, we explored the hydrodynamics of the water/alkane/salts fluid confined in slit nanopores with pore walls made up of montmorillonite and kaolinite. Both montmorillonite and kaolinite surfaces remarkably restrain the movement of the water confined in nanopores. Decane molecules tend to aggregate together and transport as a cluster. Moreover, the migration of the decane cluster is faster than that of water molecules. These findings are helpful for understanding the primary migration of hydrocarbon in clayey source rocks and the geological sealing of oil by clayey cap rocks in petroleum systems.