Abstract: Studying the structure and function of rhizosphere soil microbial communities in wheat/safflower intercropping systems is of great significance for the construction of appropriate wheat/safflower intercropping patterns and regional suitability evaluation. In this study, a wheat/safflower intercropping (2∶1) pattern was set in the field, and wheat monoculture and safflower monoculture were used as controls, based on Illumina Miseq high-throughput sequencing platform. The community structure and functional changes of bacteria and fungi in the rhizosphere soil of wheat/safflower intercropping were studied, and safflower and wheat yield were measured at maturity. The results showed that the wheat/safflower intercropping land equivalent ratio was 1.01, the intercropping advantage was not obvious. The wheat and safflower intercropping increased the bacterial diversity and fungal richness of the wheat rhizosphere, but significantly decreased the bacterial richness and fungal diversity. Intercropping significantly increased bacterial diversity in the rhizosphere of safflower but decreased fungal diversity and bacterial and fungal richness in the rhizosphere of safflower. A principal coordinate analysis and equilibrium analysis of the rhizosphere soil microbial community showed that intercropping significantly changed the microbial community structure in the rhizosphere of safflower. Proteobacteria, Acidobacteria, and Bacteroidetes were the dominant bacteria in the rhizospheres of wheat and safflower, their average total proportions of relative abundances were 65.94%, 70.57%, 71.39%, and 70.07% for monocultured wheat, intercropped wheat, monocultured safflower and intercropped safflower, respectively. Ascomycota and Basidiomycota were the dominant fungi, the their average total proportions of relative abundances were 75.99%, 68.17%, 93.23% and 69.88% for monocultured wheat, intercropped wheat, monocultured safflower and intercropped safflower, respectively. Intercropping significantly increased the relative abundance of Acidobacteria, Rokubacteria, and Mortierellomycota in the rhizosphere of safflower, while it had no significant effect on wheat. Our functional prediction results showed that intercropping significantly improved nutrient cycling processes, such as ammonia oxidation, nitrification, fermentation, and nitrate reduction in the rhizosphere of safflower. Combined with the correlation analysis results, MND1 genus of bacteria was significantly positively correlated with these processes, and its relative abundance in the rhizosphere of safflower was significantly higher in intercropping than in the monoculture. In addition, intercropping significantly increased the relative abundance of arbuscular mycorrhizal functional genes in the rhizosphere of safflower, and significantly decreased the relative abundance of plant pathogenic functional genes. At the genus level, intercropping significantly increased the relative abundance of beneficial bacteria, such as Moralella and Wickerhamomyces, in the rhizosphere of safflower. The relative abundances of pathogenic fungi belonging to Fusarium and Alternaria was significantly decreased. In conclusion, under a wheat/safflower intercropping system, safflower at a competitive disadvantage can improve the rhizosphere microbial community composition and nutrient cycling process, thus alleviating the disadvantage of nutrient competition. The co-occurrence network analysis results showed that intercropping could improve the complexity of the rhizosphere microbial network of wheat and reduce the complexity of the rhizosphere microbial network of safflower, to some extent. In addition, Fusarium is located in the center of the rhizosphere microbial network of safflower, and intercropping can significantly reduce the number of Fusarium species by affecting the interactions between the rhizosphere microorganisms of safflower. Lastly, intercropping significantly reduced the relative abundance of pathogens in the rhizosphere of safflower, which was of great significance in reducing the occurrence of safflower diseases and the total number of pathogens in the soil.