The fungal pathogenMagnaporthe oryzaesecretes a large number of effector proteins to facilitate infection, most of which are not functionally characterized. We selected potential candidate effector genes from the genome ofM. oryzae, field isolate P131, and cloned 69 putative effector genes for functional screening. Utilizing a rice protoplast transient expression system, we identified that four candidate effector genes,GAS1,BAS2,MoCEP1andMoCEP2induced cell death in rice. In particular,MoCEP2also induced cell death inNicotiana benthamianaleaves through Agrobacteria-mediated transient gene expression. We further identified that six candidate effector genes,MoCEP3toMoCEP8, suppress flg22-induced ROS burst inN. benthamianaleaves upon transient expression. These effector genes were highly expressed at a different stage afterM. oryzaeinfection. We successfully knocked out five genes inM. oryzae,MoCEP1,MoCEP2,MoCEP3,MoCEP5andMoCEP7. The virulence tests suggested that the deletion mutants ofMoCEP2,MoCEP3andMoCEP5showed reduced virulence on rice and barley plants. Therefore, those genes play an important role in pathogenicity.