Abstract: Prodigiosin is mainly produced by Serratia marcescens, and it is one of the most important secondary metabolic products in microorganisms, which belongs to lipopolysaccharide and is a typical alkaloid too. It has many physiological activities such as anti-cancer, bacteriostatic, immune-enhancing, anti-protozoal, anti-malarial,and it is an emerging and indispensable ingredient in the fields of cosmetics, dyes and water pollution control. With the continuous development of the pharmaceutical industry, industry and agriculture, the application of prodigiosin is increasing, whose good application prospect makes its synthesis and extraction process become a research hotspot in the field of secondary metabolism. However, at present, the total chemical synthesis and fermentation production of prodigiosin are affected significantly by many factors, which have greatly hindered its large-scale production and application for decades. In this paper, the factors that affect the biosynthesis of prodigiosin were reviewed, and the possible mechanism was summarized. This review showed that the factors such as bacteria species, nutritional conditions, environmental factors（including culture temperature, pH value, dissolved oxygen,illumination） and metal ions were all very important to the synthesis of prodigiosin during microbial fermentation.In addition, combined with genetic engineering and other technologies, the yield of prodigiosin could be greatly increased. This review provided an important basis for the industrial fermentation production of prodigiosin.