Combining density functional theory calculation with experiments and kinetics simulation, a multiscale framework describing the influence of reactant-substrate interaction on electrochemical performance was proposed. It was found that the close band center and the rapid adsorption kinetics facilitated the highly selective response of Ni(111) toward Cu(ii), providing a useful tactic to investigate the mechanism of electro-selectivity. This work not only verified that the interaction strength in the ex situ conditions, and kinetics rate could be applied to evaluate the electrochemical selectivity, but also contributed to the options and forecasting of selective electrode materials for heavy metal ions.