Salinomycin, an important antibiotic widely used in animal husbandry, is a potential drug with anti-tumor stem cell effect. Its biosynthesis and metabolic regulation mechanism have received increasing attention. In this paper, we reviewed the biosynthesis mechanism of salinomycin in Streptomyces albus and the recent progress in the study of its secondary metabolism regulation, aiming to propose some strategies to improve salinomycin production through secondary metabolism regulation technology by analyzing the key proteins of salinomycin biosynthesis gene cluster, key enzymes and regulatory factors of polyketone skeleton chain synthesis. It provides reference for further development of high-yield salinomycin industrial strains.