Downy mildew is an important systemic disease that reduces the yield and quality of foxtail millet. In the process of foxtail millet resisting to pathogen, resistance genes play a particularly important role. Chitinases (EC,3.2.1.14) are important pathogenesis-related protein families in plant disease resistance. They play a key role in the process of plant defense against pathogen and pest damage. In this study, based on the transcriptome analysis of Sclerospora graminicola-infected resistant and susceptible foxtail millet varieties in the early-stage, it was found that the chitinase family genes were significantly differentially expressed in resistant and susceptible varieties. It is speculated that this family genes might be involved in the regulation of foxtail millet resistance. Therefore, we performed series of bioinformatics assays and experiments on these genes. The locations of 30 selected chitinase family genes in chromosomes were revealed by bioinformatics techniques. TBtools and other software were used to analyze the physical and chemical properties, gene structure, phylogenetic tree construction, protein conserved domain. Transcriptional expressions of chitinase genes were measured by quantitative PCR. The results showed that 30 chitinase genes were distributed on 8 chromosomes except chromosome 6. All chitinase proteins are predicated to be secreted proteins and they all have conserved motifs. Phylogenetic tree analysis revealed that the gene family members could be divided into three subgroups. Combined with the transcriptome data of resistant and susceptible varieties infected by S.graminicola, the expression of up-regulated and down-regulated genes were divided into three expression modes. The results of fluorescence quantitative PCR showed that Seita.1G225300, Seita.4G286000, Seita.5G389900, Seita.7G150600, Seita.7G150700 and Seita.8G076900 were significantly differentially expressed and most likely to be involved in S.graminicola and their expression trends were consistent with transcriptome data. The results are expected to provide a theoretical reference for cloning and molecular breeding of resistance genes in foxtail millet.