To explore the effect of hypoxia on postmortem muscle aging in yaks， the expressions of phosphorylated protein kinase (p-Akt)， hypoxia-inducible factor (HIF-1α)， and ryanodine receptor (RyR) were investigated. Additionally， the regulatory roles of endoplasmic reticulum(ER) Ca2+ release and adenosine monophosphate-activated protein kinase (AMPK) activity on the tenderness of yak meat were studied. The results showed that hypoxia increased the expressions of p-Akt and HIF-1α， while in the LY294002 + Wortmannin treatment group， the expressions of p-Akt and HIF-1α were significantly decreased， indicating that the PI3K/Akt signaling pathway was involved in the regulation of HIF-1α expression. Meanwhile， the expression of RyR increased with the increase of HIF-1α expression and decreased synchronously when HIF-1α expression was inhibited (P<0.05). Moreover， with the increase of HIF-1α expression， AMPK activity and CaMKKβ expression significantly increased (P<0.05). The expression of mitochondrial permeability transition pore (MPTP) gradually increased within the first 12 h and then decreased. With the increase of HIF-1α expression， mitochondrial Ca2+ concentration and apoptosis rate decreased， while shear force increased (P<0.05). Conclusion: The PI3K/Akt signaling pathway induced by hypoxia leads to the accumulation of HIF-1α. HIF-1α mediates the inhibition of Ca2+ release， which in turn inhibits the apoptosis of muscle cells during the post-mortem maturation process of yaks， resulting in a deterioration of the tenderness of yak meat.