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Pathogenic fungi secrete numerous effectors into host cells to manipulate plants’ defense mechanisms. <i>Valsa mali</i>, a necrotrophic fungus, severely impacts apple production in China due to the occurrence of Valsa canker. Here, we predicted 210 candidate effector protein (CEP)-encoding genes from <i>V. mali</i>. The transcriptome analysis revealed that 146 CEP-encoding genes were differentially expressed during the infection of the host, <i>Malus sieversii</i>. Proteome analysis showed that 27 CEPs were differentially regulated during the infection stages. Overall, 25 of the 146 differentially expressed CEP-encoding genes were randomly selected to be transiently expressed in <i>Nicotiana benthamiana</i>. Pathogenicity analysis showed that the transient expression of VM1G-05058 suppressed BAX-triggered cell death while the expression of VM1G-10148 and VM1G-00140 caused cell death in <i>N. benthamiana</i>. In conclusion, by using multi-omics analysis, we identified potential effector candidates for further evaluation in vivo. Our results will provide new insights into the investigation of virulent mechanisms of <i>V. mali</i>.