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Isochorismate synthase (ICS) plays an essential role in the accumulation of salicylic acid (SA) and plant disease resistance.Diseases caused by Botryosphaeria dothidea affect apple yields.Thus,it is important to understand the role of ICS1 in disease resistance to B.dothidea in apple.In this study,SA treatment enhanced the resistance to B.dothidea.MdlCS1 was induced by B.dothidea and enhanced the resistance to B.dothidea.MdlCS1 promoter analysis indicated that the W-box was vital for the response to B.dothidea treatment.MdWRKY15 was found to interact with the W-box using yeast one-hybrid screening.Subsequently,the interaction was confirmed by EMSA,yeast one-hybrid,ChlP-PCR,and quantitative PCR assays.Moreover,luciferase and GUS analysis further indicated that MdlCS1 was transcriptionally activated by MdWRKY15.Finally,we found the function of MdWRKY6 in the resistance to B.dothidea was partially dependent on MdlCS1 from the phenotype of transgenic apples and calli.In summary,we revealed that MdWRKY15 activated the transcription of MdlCS1 by directly binding to its promoter to increase the accumulation of SA and the expression of disease-related genes,thereby resulting in the enhanced resistance to B.dothidea in the SA biosynthesis pathway.