A direct liquid organic hydrogen carrier fuel cell, such as the direct isopropanol fuel cell (DIFC), employs hydrogen to generate electricity through a combined process of dehydrogenation and hydrogen utilization. However, the performance decay of DIFC over time is a critical limitation. While the origin of deactivation and the strategy to overcome it have been investigated, the lack of understanding of the deactivation mechanism remains a significant bottleneck. In this study, cyclic voltammograms conducted in the half-cell (three-electrode system) exhibit a notable variation trend of degradation in isopropyl alcohol (IPA) oxidation depending on the potential window. This variation suggests surface cleaning processes based on acetone removal involving acetone oxidation and reduction, respectively. Based on this trend, a self-cleaning strategy via mixed potential between H-2 oxidation and acetone reduction is designed to remove poisoned acetone in the DIFC full-cell (two-electrode system). The enhanced durability observed in the modified DIFC, fueled by H-2-saturated IPA, validates the self-cleaning process of the electrocatalyst in the anode, suggesting the feasibility of applying the mixed potential concept to enhance durability in full-cell systems.