Objective：To detect the expression of sterile alpha motif domain-containing protein 13（SAMD13）in glioma tissues and cells，and explore the effect of SAMD13 expression on the proliferation and invasion of glioma cells，as well as the underlying regulatory mechanisms. Methods：The expression and prognosis correlation of SAMD13 in glioma patients was analyzed using GEPIA database. The expression of SAMD13 in glioma cell lines（U373，U87，and U251）was examined by RT -PCR and Western blot. The SAMD13 overexpression plasmid（pIRES2- SAMD13）and SAMD13 shRNA plasmid（shSAMD13）were constructed and transfected into cells. Western blot，CCK-8，and Transwell assays were performed to assess the effects of SAMD13 overexpression and silencing on U373 cell proliferation and invasion，as well as to evaluate the expression and phosphorylation levels of Akt1，ERK1/2，and STAT3. Additionally，the ERK1/2 inhibitor（U0126）was added during pIRES2- SAMD13 transfection to further investigate cell proliferation and invasion via CCK-8 and Transwell assays. Results：AMD13 expression was significantly higher in glioma tumor tissues，compared with adjacent normal tissues，and it was closely associated with poor prognosis in patients. SAMD13 was expressed in all three glioma cell lines（U373，U87，and U251），with the highest expression in U373 cells. In U373 cells，transfection with pIRES2-SAMD13 and shSAMD13 successfully overexpressed and silenced SAMD13，respectively，which promoted and inhibited cell proliferation and invasion，respectively. Moreover，SAMD13 overexpression significantly enhanced ERK1/2 phosphorylation，while silencing SAMD13 reduced it，with no significant effects on Akt1 or STAT3 phosphorylation. The ERK1/2 inhibitor markedly suppressed the U373 cell proliferation and invasion induced by SAMD13 overexpression，but did not affect SAMD13 expression. Conclusion：SAMD13 is highly expressed in both glioma tissues and cells，and its upregulation promotes glioma cell proliferation and invasion by activating ERK1/2 .