Pterygium is a common ocular surface disease which could result in various ocular surface symptoms. MicroRNAs play an important role in the development of various eye diseases. However, the role of microRNAs in the pathogenesis of pterygium is rarely reported. Our research aims to analyze the relationship between miR-218-5p and Epidermal Growth Factor Receptor (EGFR) in human pterygium tissues and cultured Human Pterygium Epithelial Cells (hPECs). Furthermore, the EGFR/PI3K/Akt/mTOR signaling pathway was firstly verified in pterygium. Pterygium tissues and normal bulbar conjunctival tissues were obtained from surgery, and primary hPECs were cultured in vitro. Cell transfection, Quantitative real-time PCR (qRT-PCR), Western blotting, Luciferase reporter assay and Scratch Wound Healing Assay were performed. Our data demonstrated that miR-218-5p was decreased and EGFR was increased in pterygium tissues than normal conjunctival tissues. In transfected hPECs, our results indicated that upregulated miR-218-5p significantly suppressed the expression level of EGFR via PI3K/Akt/mTOR pathway. In addition, the migration and proliferation of hPECs was promoted by miR-218-5p inhibitor and retarded by miR-218-5p mimics. And knockdown of EGFR significantly inhibit hPECs migration. Taken together, miR-218-5p downregulated the expression of EGFR via PI3K/Akt/mTOR pathway in pterygium tissues and hPECs and inhibited hPECs migration and proliferation. The microRNA-218-5p-EGFR-PI3K/Akt/mTOR axis should be further investigated for the potential treatment of pterygium.