Medulloblastoma is the most common malignant brain tumor in children. Despite remarkable advances over previous decades, the long-term survival of patients with medulloblastoma remains poor due to the frequent metastatic nature of this malignancy. The aim of the present study was to examine the role of tripartite motif containing 59 (TRIM59) in cell metastasis in medulloblastoma. It was initially demonstrated that TRIM59 expression was significantly increased in clinical medulloblastoma tissues compared with adjacent non-cancerous tissues and differentially expressed in a series of medulloblastoma cell lines. The knockdown of TRIM59 in D283 cells resulted in epithelial-to-mesenchymal transition (EMT), and decreased cell migratory and invasive capacities. By contrast, the overexpression of TRIM59 in Daoy cells was able to inhibit the EMT process and increase migratory and invasive capacities of the cells. Notably, the knockdown of TRIM59 was able to decrease the protein level of matrix metalloproteinase (MMP)-2 without altering the levels of MMP-9, and conversely the overexpression of TRIM59 was able to increase the protein level of MMP-2. Importantly, the downregulation of TRIM59 in D283 cells was able to inhibit the levels of phosphorylated (p)-AKT (Ser473), glycogen synthase kinase 3 β(GSK3β; Ser9) and phosphoinositide 3-kinase (PI3K) p85 (Tyr458) without altering the levels of total protein. The data from the present study suggest that TRIM59 induces epithelial-to-mesenchymal transition and promotes migration and invasion by PI3K/AKT signaling pathway in medulloblastoma. This data may provide novel insight into tumor metastasis and pave the way for the development of therapeutic strategies for the treatment of medulloblastoma in the clinic.