Background: Gray mold, caused by Botrytis cinerea, is one of the major fungal diseases in agriculture. Biological methods are preferred over chemical fungicides to control gray mold since they are less toxicto the environment and could induce the resistance to pathogens in plants. In this work, we try tounderstand if ginseng defense to B. cinerea could be induced by fungal hypovirulent strain △BcSpd1. BcSpd1 encodes Zn(II)2Cys6 transcription factor which regulates fungal pathogenicity and we recentlyreported △BcSpd1 mutants reduced fungal virulence. Methods: We performed transcriptomic analysis of the host to investigate the induced defense responseof ginseng treated by B. cinerea △BcSpd1. The metabolites in ginseng flavonoids pathway were determinedby UPLC-ESI-MS/MS and the antifungal activates were then performed. Results: We found that △BcSpd1 enhanced the ginseng defense response when applied to healthyginseng leaves and further changed the metabolism of flavonoids. Compared with untreated plants, theapplication of △BcSpd1 on ginseng leaves significantly increased the accumulation of p-coumaric acidand myricetin, which could inhibit the fungal growth. Conclusion: B. cinerea△BcSpd1 could effectively induce the medicinal plant defense and is referred to asthe biological control agent in ginseng disease management.