Glioblastoma multiforme (GBM), one of the most aggressive human malignant brain tumors, is induced by multiple complex pathological mechanisms. The main cause of mortality in patients with GBM is the invasion-metastasis cascade of tumor cells. The dysfunction of Parkinson protein 2 E3 ubiquitin protein ligase (PARK2) is closely linked with the development of certain human cancers. However, whether PARK2 is associated with metastasis in GBM remains unknown. The present study demonstrated that the metastasis and invasion of U87 cells were significantly repressed by PARK2 overexpression. Conversely, knockdown of PARK2 facilitated the metastasis and invasion of A172 cells. Furthermore, PARK2 downregulated zinc finger E-box-binding homeobox 1 (ZEB1) expression and mitigated epithelial-mesenchymal transition (EMT). Promoter effects of PARK2 knockdown on cell metastasis and EMT were antagonized by silencing ZEB1 expression. These results indicated that PARK2 participated in regulating the invasion-metastasis cascade of cancer cells by depressing ZEB1 expression and acting as a metastasis suppressor in GBM progression, providing a potential therapeutic approach for GBM treatment.