As the main regulator of cartilage development, Sox9 gene can initiate transcription and expression of various enzymes and protein genes required for car- tilage growth and development. During this process, the expression and function of Sex9 are also regulated by a variety of factors and signaling pathways. More re- search is concerned about the positive regulation. At present, some studies dis- closed that negative regulation of Sox9 expression existed unique mechanisms. This study will discuss and summarize the negative regulatory mechanism of Sox9 gene by microRNA, NF-κB, Wnt, Notch and other factors and signaling pathways, in or- der to provide the basic framework for further investigating the expression and func- tion of Sox9 in cartilage development.