Valsa canker caused by the necrotrophic ascomycete Valsa mali is a destructive disease on apple in eastern Asia. To date, the disease still cannot be effectively controlled, mainly because V. mali extensively penetrates into the phloem and xylem and limited information about the resistance mechanism is available. In this study, we analyzed the transcriptome of V. mali-infected apple (Malus x domestica) to identify genes associated with V. mali induced resistance responses. Totally, 2713 apple genes were significantly up-regulated upon V. mali infection. Functional enrichment analysis showed that resistance responses were significantly over-represented in up-regulated genes, including chitin, hormone and cell death responses. Two chitin-elicitor receptors, MDP0000136494 and MDP0000169047, probably were the key chitin receptors responded to V. mali-infection. Jasmonic acid and salicylic acid signaling were revealed to be the primary phytohormone pathways of apple against V. mali. In addition, 11 cytochrome P450 genes likely to be involved in the xenobiotics biodegradation or phytoalexins biosynthesis were identified. This new information provides insights into the resistance responses against V. mali. Functional verification of these genes identified here will facilitate understanding the resistance mechanism of apple and establishing new effective disease arrangement strategies.