Previous work from our laboratory identified YggX as a protein whose accumulation increased the resistance of Salmonella enterica to superoxide stress, reversed defects attributed to oxidized [Fe-S] clusters, and decreased the spontaneous mutation frequency of the cells. Here we present work aimed at determining why the accumulation of YggX correlates with reduced mutation frequency. Genetic and biochemical data showed that accumulation of YggX reduced the damage to DNA by hydroxyl radicals. The ability of purified YggX to protect DNA from Fenton chemistry mediated damage in vitro and to decrease the concentration of Fe(II) ions in solution available for chelation provided a framework for the interpretation of data obtained from in vivo experiments. The interpretation of in vitro assay results, within the context of the in vivo phenotypes, was validated by a mutant variant of YggX (C7S) that was unable to function in vivo or in vitro. We propose a model, based on data presented here and reported earlier, that suggests YggX is a player in Fe(II) trafficking in bacteria.