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Filamentous fungal pathogens secrete effectors that modulate host immunity and facilitate infection. Fu-sarium graminearum is an important plant pathogen responsible for various devastating diseases. How-ever, little is known about the function of effector proteins secreted by F. graminearum. Herein, we identified several effector candidates in the F. gra-minearum secretome. Among them, the secreted ribonuclease Fg12 was highly upregulated during the early stages of F. graminearum infection in soybean;its deletion compromised the virulence of F. grami-nearum. Transient expression of Fg12 in Nicotiana benthamiana induced cell death in a light-dependent manner. Fg12 possessed ribonuclease (RNase) ac-tivity, degrading total RNA. The enzymatic activity of Fg12 was required for its cell death-promoting ef-fects. Importantly, the ability of Fg12 to induce cell death was independent of BAK1/SOBIR1, and treat-ment of soybean with recombinant Fg12 protein in-duced resistance to various pathogens, including F. graminearum and Phytophthora sojae. Overall, our results provide evidence that RNase effectors not only contribute to pathogen virulence but also induce plant cell death.