Tibetan goat and Tibetan sheep are species peculiar to Qinghai–Tibetan Plateau which is the highest plateau in the world, and have high hypoxia resistance to the extremely bad environment. Unlike monogastrics, how the genes change responding to hypoxia in ruminants remains unclear. In this study, three healthy animals of Tibetan sheep, Tibetan goat, Chuanzhong goat, and Small-tailed Han sheep were selected. The expression of factor inhibiting hypoxia-inducible factor 1 (FIH 1) hypoxia-inducible factor 1α (HIF-1α), HIF-3α, and erythropoietin (EPO) in various tissues, including heart, liver, lungs, kidney, muscle, and brain, was investigated. The EPO was observed highly expressed in all the tissues of Tibetan goats and Tibetan sheep compared with low-altitude animals, respectively, implied that higher expression of EPO may give the explanation for the hypoxia resistance of plateau animals. Besides, we also cloned the promoters of FIH-1, HIF-1α, HIF-3α, and EPO in goats and sheep, analyzed their core regions and CpG islands. Higher methylation rate was observed in HIF-1α, HIF-3α, and EPO, whereas lower methylation rate hit on FIH-1. These data may be beneficial for revealing the response mechanism to hypoxia of plateau animals.