At　present,　safety　evaluation　standards　for　nanofood　additives　are　made　based　on　the　toxic　effects　of　a　single　additive.　Since　the　size,　surface　properties　and　chemical　nature　influence　the　toxicity　of　nanomaterials,　the　toxicity　may　have　dramatically　changed　when　nanomaterials　are　used　as　food　additives　in　a　complex　system.　Herein,　we　investigated　the　combined　toxicity　of　zinc　oxide　nanoparticles　(ZnO　NPs)　and　vitamin　C　(Vc,　ascorbic　acid).　The　results　showed　that　Vc　increased　the　cytotoxicity　significantly　compared　with　that　of　the　ZnO　only　NPs.　When　the　cells　were　exposed　to　ZnO　NPs　at　a　concentration　less　than　15　mg　L-1,　or　to　Vc　at　a　concentration　less　than　300　mg　L-1,　there　was　no　significant　cytotoxicity,　both　in　the　case　of　gastric　epithelial　cell　line　(GES-1)　and　neural　stem　cells　(NSCs).　However,　when　15　mg　L-1　of　ZnO　NPs　and　300　mg　L-1　of　Vc　were　introduced　to　cells　together,　the　cell　viability　decreased　sharply　indicating　significant　cytotoxicity.　Moreover,　the　significant　increase　in　toxicity　was　also　shown　in　the　in　vivo　experiments.　The　dose　of　the　ZnO　NPs　and　Vc　used　in　the　in　vivo　study　was　calculated　according　to　the　state　of　food　and　nutrition　enhancer　standard.　After　repeated　oral　exposure　to　ZnO　NPs　plus　Vc,　the　injury　of　the　liver　and　kidneys　in　mice　has　been　indicated　by　the　change　of　these　indices.　These　findings　demonstrate　that　the　synergistic　toxicity　presented　in　a　complex　system　is　essential　for　the　toxicological　evaluation　and　safety　assessment　of　nanofood.