Osteoporosis (OP) is a kind of bone metabolic disease usually happened in middle-aged and elderly, characterized by thereduction of bone mineral density and the destruction of bone microstructure. Accompanied by a large number of bone loss, it is easy to leadto fragility fractures in various parts of the body, causing heavy family and social burden. Therefore, it is of great significance to study thebasic theory of OP and develop new drugs. With the deepening of research on the molecular mechanism of OP, relevant regulatory factorshave been discovered one after another. p53 protein is an important intracellular regulatory factor, regulating the proliferation, differentia-tion, apoptosis, autophagy and other life processes of various cells in the body. The evidence is growing that p53 plays an important role inregulating the function and metabolism of bone and may become a new target for the treatment of bone metabolic diseases including OP.