Objective: To detect the expression of sterile alpha motif domain-containing protein 13 (SAMD13) in glioma tissues and cells, and to explore the effect of SAMD13 expression on the proliferation and invasion of glioma cells and its regulatory mechanism. Methods: The expression and prognosis correlation of SAMD13 in glioma patients was analyzed using GEPIA database. The expression of SAMD13 in glioma cells (U373, U87 and U251) was examined by RT-PCR and Western blot. SAMD13 overexpressing plasmid (pIRES2-SAMD13) and SAMD13 shRNA plasmid (shSAMD13) were constructed and transfected into U373 cells, and then the effects of SAMD13 overexpression and silencing on cell proliferation and invasion as well as Akt1, ERK1/2 and STAT3 expression and phosphorylation were determined by Western blot, CCK-8 and Transwell experiments. U373 cells were treated with pIRES2-SAMD13 and ERK1/2 inhibitor (U0126) together, and then the cell proliferation and invasion were examined by CCK-8 and Transwell experiments. Results: SAMD13 expression was increased in glioma patients and was closely correlated with prognosis. SAMD13 was also expressed in U373, U87 and U251 glioma cell lines, with U373 cells being the most significant. SAMD13 overexpression by pIRES2-SAMD13 increased the proliferation and invasion of U373 cells, and SAMD13 knockdown by shSAMD13 decreased the proliferation and invasion of U373 cells. Additionally, SAMD13 overexpression and knockdown increased and decreased ERK1/2 phosphorylation, but had no significant effects on Akt1 and STAT3 phosphorylation. Furthermore, ERK1/2 inhibitor could reduce the proliferation and invasion of U373 cells induced by SAMD13 overexpression, but had no significant effects on SAMD13 expression. Conclusion: SAMD13 is highly expressed in glioma tissues and cells, and up-regulated SAMD13 activates ERK1/2 and enhances cell proliferation and invasion of glioma cells.