For acute toxicity test, zebrafish were respectively exposed to the different concentrations of nano-ZnO (0, 0.05, 0.1, 5, 10, 25, 50 mg x L(-1)) for 4, 24 and 96 h. The superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) in the liver of zebrafish were studied, and the relative expression of Bcl-2, Bax, p53 and MDM2 in liver were also determined. Anatomical structure of the zebrafish liver was determined after exposure to nano-ZnO for 7, 15 and 30 d. Compared with the control group, the liver of the experimental groups showed obvious difference in following aspects: (1) oedema, cytoplastic vacuolation, and pyknotic nucleus were observed; (2) the number of hepatic macrophages deposited and the sinus clearance were increased; (3) the MDA contents and the activity of SOD were increased; (4) however, the activity of CAT was decreased; (5) the mRNA expression level of genes Bax/Bcl-2 ratio and p53 of stressed groups were up-regulated; the mRNA expression level of gene MDM2 down-regulation can be observed in the low concentration groups while the mRNA expression level of gene MDM2 was up-regulated in the high concentration groups. The results suggested that, the oxidative damage of nano-ZnO to the zebrafish liver was caused by the increase of oxidative stress, which made the change of antioxidant enzyme activity, induced the expression of cell apoptosis genetic and cell apoptosis, and caused the change of organizational structure of liver.