High lithium nucleation overpotential on a lithiophobic matrix results in uncontrollable growth of lithium dendrites and thus restricts the wide application of lithium-metal batteries. Herein, the single-atom iron in a N-doped carbon matrix (Fe_SA-N-C) is first reported as a lithiophilic site to minimize Li nucleation overpotential from 18.6 mV to a very low value of 0.8 mV. Molecular dynamics simulations quantitatively confirmed the excellent affinity between Li ions and Fe_SA-N-C in the atomic level. Induced by the homogeneously distributed Fe_SA-N in the carbon substrate, uniform and stable metallic Li plating/stripping behaviors are realized and lithium dendrite growth is greatly suppressed. The proposed strategy of using single-atom iron as a lithiophilic site to minimize lithium nucleation overpotential opens a promising avenue for solving intrinsic problems of Li-metal-based batteries.