For human safety, efficient removal of formaldehyde in indoor environments is essential. However, removing formaldehyde from indoor environment given the temperature and moisture remains a challenge. In this study, a metal-organic framework-based single-atom iron catalyst (FeSA) is proposed as a candidate catalyst for oxidation of formaldehyde. The optimal structure between different coordination environments of FeSA was screened by density functional theory (DFT) calculation. Guided by the theoretical results, FeSA with 5 nitrogen coordination (FeSA-N5-C) was selected and prepared experimentally for evaluation. The activity tests revealed that the removal efficiency of formaldehyde reached 85.5% at 25°C and 75% relative humidity, which is not possible for traditional catalysts. More importantly, moisture boosts catalytic oxidation of formaldehyde to some extent, illustrating that FeSA-N5-C is robust for practical applications. To our knowledge, this is the first report of single-atom catalyst for catalytic oxidation of formaldehyde, opening up a new avenue for design of high activity and strongly water-resistant catalysts.