NLRC5　is　a　member　of　the　Nod-like　receptor　(NLR)　family　that　has　been　found　to　be　associated　with　the　hepatic　ischemia/reperfusion　(I/R)　injury.　However,　the　role　of　NLRC5　in　cerebral　I/R　has　not　been　fully　understood.　The　aim　of　the　current　study　was　to　evaluate　the　effects　of　NLRC5　on　primary　hippocampal　neuronal　cells　exposed　to　oxygen-glucose　deprivation/reperfusion　(OGD/R).　Our　results　showed　that　the　mRNA　and　protein　levels　of　NLRC5　were　significantly　decreased　in　OGD/R-induced　neurons.　Overexpression　of　NLRC5　caused　significant　increase　in　cell　viability,　as　well　as　decrease　in　ROS　level.　The　bax　expression　was　significantly　decreased,　while　bcl-2　expression　was　increased　in　NLRC5-overexpressing　neurons.　Furthermore,　increased　nuclear　factor　erythroid　2-related　factor　2　(Nrf2)　and　heme　oxygenase-1　(HO-1)　expression　levels　were　observed　in　neurons　transfected　with　pcDNA3.0-NLRC5.　The　mRNA　levels　of　HO-1,　NAD(P)H:quinone　oxidoreductase　1　(NQO-1)　and　glutathione　peroxidase　3　(GPx-3)　were　induced　by　NLRC5　overexpression　in　OGD/R-induced　hippocampal　neurons.　Additionally,　inhibition　of　Nrf2/HO-1　pathway　abolished　the　protective　effect　of　NLRC5　on　cerebral　I/R　injury.　In　conclusion,　these　results　indicated　that　NLRC5　protected　hippocampal　neurons　from　OGD/R-induced　injury.　The　protective　effects　of　NLRC5　were　mediated　by　the　Nrf2/HO-1　pathway.　Thus,　NLRC5　might　serve　as　an　effective　target　for　the　treatment　of　cerebral　I/R　injury.