Suffusion is the process defined as the migration of relatively small soil particles through the pores of a soil matrix composed of relatively large particles, driven by substantial hydrodynamic forces and weak attraction energies. This study investigates the influence of flow direction (upward and downward) on suffusion induced by interaction energies in sand-clay mixtures under both saturated and unsaturated conditions. The impact of clay mineralogy (kaolinite, illite, and montmorillonite), sand-grain size, and ionic concentration (IC) gradient were discussed based on the observed breakthrough curves (BTCs) and relative saturation rate (Sr) during injection (particularly for unsaturated conditions). Under saturated conditions, higher susceptibility to suffusion was observed in sand-kaolinite and sand-illite mixtures under downward flow compared to upward flow, whereas the suffusion of montmorillonite was more significant under upward flow than under downward flow. In contrast, for unsaturated conditions, more substantial suffusion of kaolinite and illite particles occurred under upward flow compared to downward flow, whereas the opposite trend was observed in sand-montmorillonite mixtures. In addition, the impact of sand-grain size (or the size ratio between sand and clay) on the suffusion of kaolinite and illite under unsaturated conditions suggests a reduced size ratio that leads to relatively significant suffusion under downward flow compared to upward flow. The findings presented in this study contribute to a comprehensive understanding of the influence of flow direction on suffusion in sand-clay mixtures under both saturated and unsaturated conditions.