Oxidative stress enhances cellular DNA oxidation and may cause mutations in DNA bases, including 8-oxogua-nine (8-oxoG). Our recent study reported that exposure of cells to non-thermal dielectric barrier discharge (DBD) plasma generates reactive oxygen species and damages DNA. The present study investigated the effect of non-thermal DBD plasma exposure on the formation of 8-oxoG in HaCaT human keratinocytes. Cells exposed to DBD plasma exhibited increased level of 8-oxoG. In addition, mRNA and protein expression levels of 8-oxoguanine glycosylase 1 (OGG1), an 8-oxoG repair enzyme, were reduced in plasma-exposed cells. Furthermore, the expression level of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates OGG1 gene expression, was reduced following exposure to DBD plasma. Pretreatment of cells with an antioxidant, N-acetyl cysteine (NAC), prior to plasma exposure suppressed the formation of 8-oxoG and restored the expression levels of OGG1 and Nrf2. In addition, phosphorylation of protein kinase B (Akt), which regulates the activation of Nrf2, was reduced following plasma exposure. However, phosphorylation was restored by pretreatment with NAC. These findings suggested that non-thermal DBD plasma exposure generates 8-oxoG via inhibition of the Akt-Nrf2-OGG1 signaling pathway in HaCaT cells.