Abstract: This study was designed to elucidate the role of oxidant response genes in the virulence of attenuated Salmonella typhimurium (ST). After ST mutants with single or multiple deletions were constructed: the susceptibility of ST to hydrogen peroxide and S-nitrosoglutathione, expression of Salmonella pathogenicity island-2 genes and the virulence of attenuated ST were assessed in this study. Unexpectedly, no difference was observed between the growth of rpoE mutant ST98 and Wild Type (WT) however, the rpoS mutant was hypersusceptible to hydrogen peroxide. The expression and Nitrogen Oxide (NO)-detoxifying activity of the flavohemoglobin hmp were associated with the mechanism of resistance of ST98 to NO. A triple mutant of ST98 in which rpoS, ssrAB and hmp genes were deleted showed a permanent phenotype with no modification of other characteristics. In a mouse infection test, the survival of ST98 triple mutant was lower than that of WT. The virulence of ST was shown to be associated with the oxidant response genes. This study provides useful information for understanding the combinational role of oxidant response genes in the virulence of Salmonella.