Background Plants are constantly threatened by various pathogens in a challenging environment. Altemaria panax Whetzel is a destructive pathogen that affects many plants, including Panax notoginseng, and significantly reduces the yield and product quality of Panax notoginseng. It is not clear how Panax notoginseng responds to pathogen infection.Methods Using the advanced advantages of transcriptome and proteomics technology, we studied the response of Panax notoginseng to Altemaria panax stress.Results Compared with the control, fungal infection caused significant changes in the Panax notoginseng transcriptome and proteome. Specifically, a total of 136,100 transcripts and 4,468 proteins were identified. The integration of transcriptome and proteome profiles revealed many candidate transcripts/proteins, which may be involved in lignin synthesis during the activation of defense responses by Panax notoginseng. Many genes and proteins are induced or inhibited by fungi. Among them, the expression levels of genes PAL, 4CL, COMT, CAD and POX in the lignin synthesis pathway are significantly increased, which indicates that the fungus activates the defense response of Panax notoginseng.Conclusions As far as we know, this is the first time that transcriptome and proteome analysis have been combined to study the response of Panax notoginseng to disease. This study provides a wide range of new information about the transcriptome, proteome and their correlation of Panax notoginseng in response to fungal stress. The analysis of this resource allows us to examine the mechanisms of transcription and protein diversification, which expands the knowledge of the complexities of the transcriptome and proteome in traditional Chinese medicines.