Oxidative　stress-induced　damage　of　retinal　ganglion　cells　(RGCs)　is　a　major　contributor　to　retinal　degenerative　diseases,　such　as　glaucoma.　Sirtuin　6　(SIRT6)　has　emerged　as　a　cytoprotective　protein　against　various　insults.　However,　whether　SIRT6　exerts　a　protective　effect　against　oxidative　stress-damaged　RGCs　remains　unknown.　In　this　study,　we　aimed　to　investigate　the　potential　role　and　regulatory　mechanism　of　SIRT6　in　hydrogen　peroxide　(H＜sub＞2＜/sub＞O＜sub＞2＜/sub＞)-induced　oxidative　damage　of　RGCs　in　vitro.　We　found　that　SIRT6　expression　was　significantly　downregulated　in　RGCs　with　H＜sub＞2＜/sub＞O＜sub＞2＜/sub＞　treatment.　Functional　experiments　showed　that　overexpression　of　SIRT6　improved　survival　and　reduced　apoptosis　and　the　production　of　reactive　oxygen　species　(ROS)　in　H＜sub＞2＜/sub＞O＜sub＞2＜/sub＞-treated　RGCs.　In　contrast,　SIRT6　knockdown　had　the　opposite　effect.　Moreover,　we　found　that　SIRT6　overexpression　promoted　the　nuclear　accumulation　of　nuclear　factor　erythroid　2-related　factor　2　(Nrf2)　and　increased　the　activity　of　antioxidant　response　element　(ARE).　In　addition,　we　found　that　the　promotional　effect　of　SIRT6　on　Nrf2/ARE　signaling　was　associated　with　inhibition　of　BTB　and　CNC　homology　1　(Bach1),　an　inhibitor　of　Nrf2.　However,　overexpression　of　Bach1　or　inhibition　of　Nrf2/ARE　signaling　partially　reversed　the　SIRT6-mediated　protective　effect.　Taken　together,　these　results　demonstrate　that　SIRT6　protects　RGCs　from　oxidative　stress-induced　damage　by　promoting　the　activation　of　Nrf2/ARE　signaling　via　inhibition　of　Bach1,　suggesting　a　potential　role　of　SIRT6　in　retinal　degenerative　diseases.