Abstract: 【Objective】The purpose was to study the core genes of wheat cultivar Lianmai 12 in response to Fusarium graminearum infection， and provide theoretical bases for the defense molecular network in wheat fusarium head blight. 【Method】The transcriptome of Lianmai 12 spikelets， which successfully infected with F. graminearum， was sequenced. Screening differentially expressed genes（DEGs）through DESeq， conducting GO functional annotation and KEGG signaling pathway enrichment analysis. The protein-protein interaction network based on DEGs were constructed. Core genes were screened by MCODE and cytoHubba.【Result】After 72 h of inoculation with F. graminearum（treatment group）and sterile deionized water（control， CK）in Lianmai 12， a total of 14180 DEGs were screened， among which 10966 DEGs were up-regulated and 3214 DEGs were down-regulated. According to GO functional annotation， the could be divided into 3 major categories and 51 items. The cell components contained 14 items， mainly enriched in 3 items：cell， cell part and membrane. The molecular function included 11 items， mainly enriched in 2 items： catalytic activity and binding. Biological process include 26 items， mainly enriched in 3 items：cellular process， metabolic process， and response to stimulus. KEGG annotated the largest number of differential genes in metabolic pathways， biosynthesis of secondary metabolites， phenylpropanoid biosynthesis， plant hormone signal transduction and plant MAPK signaling pathways. KEGG pathway mostly enriched in photosynthesis-antenna proteins，phenylalanine，tyrosine and tryptophan biosynthesis，glutathione metabolism， flavone and flavonol biosynthesis and linoleic acid metabolism. Protein-protein interaction network was constructed with a combined score＞0.7， and a total of 258 up-regulated main DEGs were screened. Important gene interaction module was constructed and screened by MCODE clustering， which obtained 2 important gene function modules containing 13（score=7.67）and 6（score=5.60）important DEGs respectively. The 10 core genes screened by cytoHubba， based on most closely interacting proteins， were coincided with the MCODE screening. The 10 core genes expression trends which verified by fluorescence quantification were basically consistent with the expression trends of transcriptome sequencing.【Conclusion】The expression of 10 core genes are all up-regulated after F. graminearum infection， which speculates that these 10 core genes play an important role in the response of Lianmai 12 to F. graminearum infection.