Metal ions play important roles in various biological processes of living systems. However, the generation of reactive oxygen species (ROS) is also closely linked with the participation of redox-active metal ions such as copper, iron, chromium, and cobalt ions. Excessive production of ROS by redox-active metal ions can cause oxidative stress and further oxidative stress-related diseases. This study shows the results of the antioxidant activity of kaempferol in both $ORAC_{OH{cdot}}$ and $Cu^{2+}$-treated HepG2 cells. Preventive mechanism of kaempferol in $Cu^{2+}$-treated HepG2 cells is also elucidated. These results suggest that both cellular $Cu^{2+}$-chelating activity and expression of phase II detoxifying enzymes such as HO-1 and GSTA2 through activating Nrf2 are required for cellular antioxidant activity of kaempferol in $Cu^{2+}$-treated HepG2 cells. Our findings provide the scientific evidence for the development of Nrf2 targeting dietary antioxidant to prevent oxidative stressrelated conditions.