Oxygen is an environmental and developmental signal regulator, involved in energy homeostasis, development and process of differentiation. Myoblasts persist in skeletal muscle as satellite cells, which possess capability of self-renewing and differentiation into mature myofiber. Myoblasts play an important role in postnatal muscle regeneration after injury as well as maintaining myofibers function. Though oxygen is vital to nearly all forms of life, little is known on the effects of oxygen level on proliferation and differentiation of myoblasts. The level of oxygen in physiological and pathological microenvironment in vivo is low. This review summarizes recent advances in the study of the effects of hypoxia on proliferation and differentiation of myoblasts and HIF signaling pathway involved in these processes.