RNA polymerase I (Pol I) is a multi-subunit protein complex associated with the transcription of most ribosomal RNA molecules in all eukaryotes. Rpa12 is a small subunit of the Pol I catalytic core and plays a critical role in RNA cleavage, transcription initiation and elongation during proliferation in yeast and mammals. However, the function of Rpa12 in phytopathogenic fungi has not yet been characterized. Here, we present the functional characterization of MoRpa12, a homologue of the yeast Rpa12, in Magnaporthe oryzae. MoRpa12 shows upregulation during the infection phase, and MoRpa12-GFP exhibits nuclear localization at different developmental stages of M. oryzae and translocates into the nuclei of plant cells after fungal penetration. The MoRpa12 mutants also exhibit significant defects on mitosis, autophagy, oxidative stress tolerance, cell wall integrity, septin ring assembly, lipid and glycogen metabolism, and pathogenicity. The four cysteine residues at the amino terminus of this protein are critical for the nuclear localization of MoRpa12, and their site-directed mutagenesis affects the localization, fungal invasion, and full virulence of M. oryzae. In conclusion, our findings indicate that MoRpa12 functions as an unconventional secreted effector targeting host nuclei and is essential for the fungal growth and plant infection of M. oryzae.