Altered oxidative metabolism is a property of many tumor cells. Oxidation of dNTP pool as well as DNA is a source of genome instability. We report here that two Y-family DNA polymerases of the archaeon Sulfolobus solfataricus strains P1 and P2 incorporate oxidized dNTPs into nascent DNA in an erroneous manner: the polymerases exclusively incorporate 8-hydroxy-dGTP opposite template A, and incorporate 2-hydroxy-dATP opposite G and T. Extension onto the incorporated analogs is only slightly reduced. Human DNA polymerase η, a member of human Y-family DNA polymerases, incorporates the oxidized dNTPs in a similar erroneous manner. These DNA polymerases are shown to bypass a variety of DNA lesions. Thus, our results suggest the Y-family DNA polymerases promote mutagenesis through the erroneous incorporation of the oxidized dNTPs during DNA synthesis in addition to facilitating translesion DNA synthesis.