Abstract: In the present study, embryo liver tissues collected from hypoxic incubation of Tibet chicken and Shouguang chicken were analyzed on their histological structures and antioxidant capacity as well as differential proteomics to study the mechanism of Tibet chicken’s adaptability to hypoxia. The results of histological study conducted with paraffin and ultrathin sections showed that Shouguang chicken had a weaker liver structure with less cell layers and the development of its liver was more impaired compared with Tibet chicken and Tibet chicken maintained relatively better mitochondria than Shouguang chicken. The content of Maleic dialdehyde in Tibet chicken was lower than Shougguang chicken, but the total antioxidant capacity and the content of Superoxide Dismutase in Tibet chicken were higher than Shouguang chicken. Using two-dimensional electrophoresis and mass spectrometry, we identified 8 differential expression liver proteins between Tibet chicken and Shouguang chicken, in which 6 proteins (enolase I, pyruvate dehydrogenase, ATP synthase, ubiquinol-cytochrome C reductase, superoxide dismutase and apolipoprotein A-I) showed higher expression level in Tibet chicken than that in Shouguang chicken while the expressions of the other 2 proteins (Triose phosphate isomerase, adenosine 5-diphosphosugar pyrophosphatase) were less in livers of Tibet chicken. These results indicated that Tibet chicken had higher glucose oxidation level, electron transfer efficiency and antioxidant ability than Shouguang chicken under the hypoxic condition and these differences made Tibet chicken have better adaptability to hypoxia than Lowland chicken. The study made a good basis for the further study of the genetic mechanism of adaptation to hypoxia.