Objective To investigate the protective effect ofβ- catenin gene in hepatic ischemia- reperfusion injury among mice and the underlying mechanism. Methods Using β- catenin knockout mice and a segmental hepatic ischemia- reperfusion model, serum levels of alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) and the pathological changes in the liver were evaluated after segmental hepatic ischemia- reperfusion, and the mRNA expression levels of hypoxia- inducible factor 1α ( HIF- 1α) , tumor necrosis factor- α ( TNFα) , and interleukin- 1β ( IL- 1β) in the liver tissues of β- catenin- /-mice and wild- type ( WT) mice were determined by real- time fluorescence quantitative polymerase chain reaction six hours after reperfusion. Comparisons between groups were performed with the t test or analysis of variance. Results β- catenin- /-mice sustained severer pathological injury from ischemia- reperfusion than WT mice, as evidenced by significantly higher serum levels of ALT ( 8178. 61 ± 78. 76 U / L vs 891. 83 ± 23. 73 U / L, t = 24. 296, P < 0. 001) and AST ( 7348. 94 ± 141. 99 U / L vs 873. 50 ± 20. 27 U / L, t = 27. 854, P < 0. 001) and significantly higher mRNA expression levels of TNF- α ( 3. 14 ± 0. 37 vs 1. 00 ± 0. 19, t = 3. 676, P < 0. 01) and IL- 1β ( 3. 72 ± 0. 33 vs 1. 00 ± 0. 24, t = 4. 017, P < 0. 01) in β-catenin- /-mice compared with WT mice. In contrast, the mRNA expression of HIF- 1α was down- regulated in β- catenin- /-mice relative to WT mice ( 0. 31 ± 0. 04 vs 1. 00 ± 0. 22, t = 3. 949, P < 0. 01) . Conclusion β- catenin gene deletion aggravates hepatic ischemia- reperfusion injury by reducing the expression of HIF- 1α.