Valsa canker is a fungal disease of apple and pear growing areas in China even Asia. Malectin like kinases take crucial roles in plant recognition of the pathogen-induced signals and subsequent activation of partially host immune responses. However, the role of MEDOS1 (MDS1) in plant immunity has not yet been extensively explored. In the Malus domestic genome, we found that the MdMDS1, a homologous gene of MDS1 in Arabidopsis, responded to Valsa mali ( Vm) and Valsa pyri ( Vp). Over-expression of MdMDS1 decreased Valsa canker resistance of Pyrus betulifolia ‘Duli-G03’ suspension cells, and apple and pear fruits. During suspension cells in response to Vp signals, up-regulation of MdMDS1 inhibited expression of defense-related genes but activated cell wall related genes. Among these, pectin methylesterase gene PbePME1 was robustly induced. Further analysis confirmed that PbePME1, a negative regulator of Valsa canker resistance, was indispensable for MdMDS1’s function by interaction. Our results provide a theoretical reference for the resistant breeding and comprehensive control of Valsa canker of both apple and pear.