MnSOD and catalase are endogeneous antioksidants which function to neutralize free radicals. Oxydative stress causes oxidative damage which can be measured by elevated levels of Malondialdehyde (MDA) in the cells. Chronic systemic hypoxia is a condition caused by a systemic decrease in oxygen intake in the long term. This condition can cause oxidative stress that result in oxidative damage to cells in various tissues. Our previous study proved that there are different responses in different rat tissues induced chronic systemic hypoxia. The objective of this study was to analyze specific activity of MnSOD and catalase in mouse liver tissue induced with systemic hipoksia and their association with oxidative damage. Sample in this research is male mouse liver tissue from Sprague Dawley strain (Rattus novergicus L), induced with chronic systemic hypoxia for 1,7,14 and 21 days. Mouse liver homogenate tested for specific activity of MnSOD, katalase and MDA.Data showed a decline in specific activity of MnSOD and catalase are significant (p <0.05) accompanied by elevated levels of MDA on day 7 of induction of systemic hypoxia. Also obtained a negative relationship between the specific activity of MnSOD and catalase with the levels of MDA, so that MnSOD and catalase thought to play a role in preventing oxidative damage to lipids in liver cells. From the results of this study can be concluded that the induction of systemic hypoxia of up to 7 days cause oxidative damage to liver cells characterized by increased MDA and followed by a response decrease in antioxidant activity of MnSOD and catalase