Hydrogen peroxide oxidizes RhoA at Cys16 and Cys20 and activates RhoA via Vav2. The oxidized RhoA is dissociated from RhoGDI. Oxidized RhoA binds to IKKγ and activates the adjacent IKKβ, thereby leading to NF-κB activation. Hydrogen peroxide stimulates cell proliferation and tumorigenesis through RhoA oxidation.