Protein arginine methyltransferase 5 (PRMT5) is a major type II arginine methyltransferase that catalyzes the formation of symmetric dimethylarginine in a number of nuclear and cytoplasmic proteins. PRMT5 plays a critical role in regulating biological processes including transcription, cell cycle progression, RNA splicing, and DNA repair. Currently, an increasing number of studies have identified the roles of PRMT5 as a tumor-promoting factor in several cancers. PRMT5 promotes the carcinogenicity of various solid tumors including colon, breast, prostate, lung, liver, bone, ovarian, gastric, and pancreatic cancers with poor clinical outcomes. In recent years, novel inhibitors of the PRMT5/MTA complex have been developed for the treatment of MTAP-deleted cancers.