There are increasing evidence showing that microorganisms in interlayer oxidation zone sandstone type uranium deposit have involved in uranium metallogeny, indicating that China should focus on study of important role of microorganisms in the formation of interlayer oxidation zone sandstone type uranium deposits. Through molecular biology, living bacterium cultivating and laboratory simulation method, this study discussed microbial relationship with uranium mineralization in the Shihongtan and Mengqiguer sandstone type uranium deposits of Xinjiang. The results show that the microbial groups have different distribution characteristics in the different geochemical environments and present distinct biogeochemical zonation. From oxidation to reduction zones, the number of anaerobic bacteria increases while the number of aerobic bacteria number decreases. The distribution of bacteria in each zone is controlled by organic carbon content, iron occurrence and content and dissolved oxygen and sulphate content in groundwater. Microbial effects on uranium mineralization are comprehensive and restricted by various environmental factors. There are kinds of relationship occurring in microorganism, such as symbiosis and mutualism, and competition and antagonism, all of which affect the development of uranium deposits. The microorganism enrichment mechanism of uranium deposits is dominated by indirect metabolic biosorption, followed by enrichment of metabolic mechanism.