Transient Receptor Potential Melastatin 7 (TRPM7) is an ubiquitously expressed cation channel that possesses unique features such as high permeability to magnesium ion, and the presence of a kinase-domain in its C-terminus. TRPM7 is known to be involved in a variety of cellular, physiological, and pathological processes including cell proliferation, embryonic development, and oxidative stress-induced cytotoxicity; however, it is still obscure whether TRPM7 plays a role in skeletal muscle. Here we show that TRPM7 plays a role in regeneration of myofibers after muscle injury. In silico analysis demonstrates that TRPM7 is predominantly expressed in muscle stem cells called muscle satellite cells (MuSCs) but not in mature myofibers. A conditional deletion of Trpm7 led to impaired myofibers regeneration after cardiotoxin-induced myofiber injury, probably due to a proliferation defect in MuSCs. Thus, our results indicate that TRPM7 is crucial for maintenance of muscle homeostasis by regulating the fate decision of MuSCs.