Designing and synthesizing efficient molecular catalysts may unlock the great challenge of controlling the CO2 reduction reaction (CO2RR) with molecular precision. Nickel phthalocyanine (NiPc) appears as a promising candidate for this task due to its adjustable Ni active-site. However, the pristine NiPc suffers from poor activity and stability for CO2RR owing to the poor CO2 adsorption and activation at the bare Ni site. Here, a ligand-tuned strategy is developed to enhance the catalytic performance and unveil the ligand effect of NiPc on CO2RR. Theoretical calculations and experimental results indicate that NiPc with electron-donating substituents (hydroxyl or amino) can induce electronic localization at the Ni site which greatly enhances the CO2 adsorption and activation. Employing the optimal catalyst-an amino-substituted NiPc-to convert CO2 into CO in a flow cell can achieve an ultrahigh activity and selectivity of 99.8% at current densities up to -400 mA cm(-2). This work offers a novel strategy to regulate the electronic structure of active sites by ligand design and discloses the ligand-directed catalysis of the tailored NiPc for highly efficient CO2RR.