Glioblastoma (GBM) is the most common primary brain tumor and the leading cause of tumor-related death in the central nervous system. To date, the mechanisms of GBM genesis remain elusive. Forkhead box protein C2 (FOXC2) is a transcription factor that has been reported in many cancers, but its function in GBM tumorigenesis is not clearly elucidated. This study found that FOXC2 was overexpressed in GBM cell lines and GBM tissues. The proliferation and invasive potential of GBM cells were significantly increased by ectopic expression of FOXC2 but significantly decreased by RNA interference targeting FOXC2. EGFR expression was modulated by FOXC2 both in mRNA and protein levels. EGFR inhibition by siRNA reversed the FOXC2-induced proliferation and invasion. These findings suggested that FOXC2 expressed in GBM has a function in GBM cell proliferation and invasion and may be partly associated with the EGFR overexpression.