This study was design to clarify the important transduction role of Ca2+ in meat tenderness development of Tan sheep during postmortem storage. Results indicated that the shear force decreased significantly before 96 h， and then increased significantly from 96-192 h. Mitochondrial Ca2+ levels increased significantly before 96 h， and decreased significantly after 96 h. The activity of calpain-1 decreased significantly with increasing time postmortem. The activity of caspase-3 increased significantly before 96 h and then decreased significantly. Correlation analysis indicated that the shear force was positively correlated with mitochondrial Ca2+ levels， and significant positively correlated with activity of caspase-3， significant negatively correlated with activity of calpain-1. 0-96 h， 5 up-regulated differentially abundant proteins and 2 down-regulated differentially abundant proteins were enriched in Ca2+ signaling pathway. 96-192 h， 2 down-regulated differentially abundant proteins were enriched in Ca2+ signaling pathway. 0-96 h， 30 differentially abundant proteins were enriched in apoptosis signal transduction pathways. 96-192 h， 15 differentially abundant proteins were enriched in apoptosis signal transduction pathways. The energy from hydrolysis of ATP was used by SERCA to drive Ca2+ transport across membranes. Increasing of VDAC likely provided channels for Ca2+ lead to mitochondrial Ca2+ overloading and mitochondrial dysfunction. Meanwhile， increasing of VDAC could be related to the increase of CYTC in cytoplasm， thereby caused the cascade of apoptosis， and activated caspase-3 to hydrolyze structural proteins， finally influence tenderness of Tan sheep meat. In addition， the decrease of actin was caused by Ca2+， and provided the contractile mechanism of muscle tissue， thus affecting the tenderness of meat. The conclusion of this study further confirmed the important signal transduction role of Ca2+ in the development of meat tenderness during postmortem storage.