Abstract: The protective effects of sodium selenite (Na₂SeO₃) on oxidative damage and apoptosis of liver cells (L8824) induced by sodium nitrite (NaNO₂) were investigated. Cells were pre-incubated by Na₂SeO₃ for 12h and then exposed to NaNO₂ (5, 10 and 25 mg/L) for 24h. The results showed that the apoptotic rate was highly induced by NaNO₂, and the activities of glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT) as well as the expressions of glutathione peroxidase (gpx), superoxide dismutase (sod) and catalase (cat) genes were reduced (P<0.05). After the cells treated by Na₂SeO₃ for 24h, the expressions of gpx, sod, cat and the activities of GPX, SOD, CAT increased (P<0.05), the expression of anti-apoptosis gene bcl-2 and the marker gene of Nrf2 pathway Keap1 up-regulated significantly. When the cells were pre-incubated by Na₂SeO₃ for 12h and then exposed to NaNO₂ for 24h, the antioxidant and apoptosis indicators could be maintained at normal levels, as well as the Nrf2 and Keap1. Na₂SeO₃ might prevent the decrease of GPX, SOD, CAT levels and the increase of apoptotic rate. The results showed that the supplement of selenium in the liver cells of grass carp could prevent the damage of antioxidant system and apoptosis-promoting caused by NaNO₂ exposure, and the Nrf2 pathway might play an important role in this process.