Collagen triple helix repeat containing 1 (CTHRC1), an extracellular matrix-related protein, has been found to be upregulated in many solid tumors and contributes to tumorigenesis. We found that CTHRC1 is overexpressed in glioblastoma tissues and cells. By using the technique of RNA interference, the expression of CTHRC1 in the human glioblastoma U-87MG cell line was downregulated, and the proliferation and migration of U-87MG cells were examined. The results showed that the knockdown of CTHRC1 exerts inhibitory effects on the proliferation and migration ability of U-87MG cells. Knockdown of CTHRC1 expression in U-87MG cells resulted in upregulation in the expression of E-cadherin and downregulation in the expression of N-cadherin, SNAIL, and Slug, suggesting that CTHRC1 inhibits glioblastoma cell migration by suppressing epithelial-mesenchymal transition (EMT). Knockdown of CTHRC1 led to remarkably decreased β-catenin protein levels in the nucleus. These results indicate that CTHRC1 might play an important role in the development of glioblastoma and offer a candidate molecular target for glioblastoma prevention and therapy.