Abstract:[Background] As a preservative added in bread and other foods, calcium propionate has a certain antimicrobial effect, but most of its current researches focus on biochemical and group levels. [Objective] To explore the mechanism of antimicrobial effect of calcium propionate on Saccharomyces cerevisiae at the molecular level. [Methods] Transcriptome sequencing and analysis were performed on logarithmic growth period of high-glucose resistant yeast BH1 in experimental group and control group, and real-time fluorescent quantitative PCR was performed for verification. [Results] Compared with the 6 h control group (no calcium propionate treatment; control group, CG), there were 1 438 differentially expressed genes (DEGs) in the 6 h experimental group (calcium propionate 2 h group, CP2G), of which 643 genes were up-regulated and 795 gene down-regulation. Compared with the 4 h experimental group (calcium propionate 0 h group, CP0G), there were 1 921 differentially expressed genes in CP2G, of which 1 438 genes were up-regulated and 483 genes were down-regulated. Among them, DEGs involved in multiple pathways, including the mitogen-activated protein kinase (MAPK) signal pathway, cell cycle pathway, and meiotic pathway. In addition, genes involved in cell wall synthesis also differentially express. [Conclusion] The molecular mechanism of calcium propionate’s antimicrobial effect on yeast was explored, which provided a theoretical basis for further revealing the mechanism of calcium propionate’s antimicrobial effect.