Objective To establish a cell model of primary neuronal hypoxic-ischemic brain injury and explore the effects of circular RNA-ZNF292 (cZNF292) on neuronal oxidative stress and apoptosis after hypoxic-ischemic brain injury.Methods The primary neurons were cultured in fetal rats on the 18^th day of pregnancy. The cells were treated with 4, 10 mmol/L Na₂S₂O₄ and glucose-free medium for 1, 2, 3 and 4 h, and reoxygenated for 0, 5, 15 and 30 h to establish the oxygen and glucose deprivation/reoxygenation cell model. The morphological changes of primary neurons were observed by immunofluorescence staining of cytoskeletal proteins and β3-tubulin, the effects of different concentrations of Na₂S₂O₄ on the survival rate of primary neurons were observed by fluorescein isothiocyanate (FITC)-phalloidin staining. The expression levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) in the culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of caspase 3 and cyclin G1 (CCNG1) were detected by Western blotting.Results The hypoxic-ischemic brain injury cell model and cZNF292-knockdown model were successfully established and the highest inhibition rate was observed in 10 mmol/L Na₂S₂O₄ and reoxygenation 4 h after deoxygenation. The expression level of cZNF292 was the highest in cells after reoxygenation culture for 15 h. Therefore, hypoxia culture for 4 h, reoxygenation culture for 15 h and 10 mmol/L Na₂S₂O₄ were selected as the best experimental conditions. Oxygen and glucose deprivation increased the levels of ROS and MDA, and decreased the levels of SOD and LDH in cell culture medium (all P < 0.05); after knockdown of cZNF292, the levels of ROS and MDA were decreased, and the levels of SOD and LDH were increased (all P < 0.05). Knockdown of cZNF292 decreased the expression of caspase 3 and CCNG1 (both P < 0.05).Conclusion Cerebral ischemia can increase expression of cZNF292 in primary neurons, while knockdown of cZNF292 can alleviate the oxidative damage, inhibit cell apoptosis and proliferation of primary neurons in the environment of ischemia and hypoxia.