Objective: To investigate the expression of mucin-4 (MUC4) in meningiomas. Methods: Totally 258 cases of meningiomas and 165 cases of other brain tumors were collected from the First Affiliated Hospital of China University of Science and Technology (Anhui Provincial Hospital) from 2011 to 2017. MUC4, EMA, PR, SSTR-2 protein expression was detected by immunohistochemistry, and their expression in meningiomas and other tumor tissue was compared. Results: The 258 patients with meningioma included 85 males and 173 females, with a mean age of 69 years. Among the meningiomas, 192, 54 and 12 were WHO grades Ⅰ, Ⅱ and Ⅲ respectively. The overall expression rate of MUC4 in meningiomas was 67.8% (175/258), including 46/46 (100.0%) in meningothelial meningiomas, 3/3 in secretory meningiomas, 44/45 (97.8%) in angiomatous meningiomas, 37/41 (90.2%) in atypical meningiomas, 3/4 in metaplastic meningiomas, 2/3 in microcystic meningiomas, 7/11 in psammomatous meningiomas, 7/11 in chordoid meningiomas, 14/28 (50.0%) in transitional meningiomas, 1/2 in clear cell meningiomas, 1/2 in papillary meningiomas, 4/9 in anaplastic meningiomas, 7/52 (13.5%) in fibrous meningiomas, and 0/1 in rhabdoid meningiomas. In addition, MUC4 was expressed in 44 EMA negative meningiomas and in four SSTR-2 negative meningiomas. PR, EMA, SSTR-2 were expressed in 149 cases (57.7%), 173 cases (67.1%), 235 cases (91.1%) of meningiomas, respectively. MUC4 was not expressed in other tumors in the central nervous system, including schwannomas, neurofibromas, solitary fibrous tumors/hemangiopericytoma (SFT/HPC), hemangioblastoma, gliomas and ependymomas. Conclusion: MUC4 is widely expressed in meningiomas and has great value in distinguishing meningiomas from other non-meningeal epithelial tumorsof the central nervous system.