Caspase recruitment domain-containing membrane-associated guanylate kinase protein 10 or CARMA3 (CARD10) is a recently characterized oncoprotein involved in the progression of several human malignancies. The present study aims to investigate the expression pattern and biological roles of CARMA3 protein in human glioma. CARMA3 expression was analyzed in 97 glioma specimens using immunohistochemistry. We observed negative staining in normal astrocytes and positive staining of CARMA3 in 25 out of 97 (25.8%) glioma samples. Overexpression of CARMA3 correlated with tumor grade (p < 0.001). Small interfering RNA knockdown was performed in A172 cell line with relatively high CARMA3 expression. Using colony formation assay and Matrigel invasion assay, we showed that CARMA3 depletion in A172 cell line inhibited cell proliferation and cell invasion. In addition, mRNA and protein levels of matrix metallopeptidase 9 (MMP9) were downregulated, indicating CARMA3 might regulate invasion through MMP9. In conclusion, CARMA3 serves as an oncoprotein in human glioma by regulating cell invasion, possibly through MMP9 regulation.