Four‐and‐a‐half‐LIM protein 2 (FHL2) is a member of FHL protein family, which plays a crucial role in regulating gene expression, cell survival, and migration. Although its function in oncogenesis appears to be tumor type‐specific, its roles in glioma formation and development are yet to be elucidated. In the present study, we demonstrated that the mRNA level of FHL2 was elevated in both low‐ and high‐grade glioma samples. Overexpression of FHL2 stimulated the proliferation, anchorage‐independent growth, and migration of human glioblastoma cells. Conversely, FHL2 knockdown by short hairpin RNA (shRNA‐FHL2) inhibited glioblastoma cell proliferation and migration. Overexpression of FHL2 increased the tumorigenicity of glioblastoma cells in nude mice and decreased the mRNA levels of p53 and its downstream proapoptotic genes, including p21, Bcl2‐associated protein X (Bax), and p53‐upregulated modulator of apoptosis. It also enhanced the promoter activities of activator protein‐1 (AP‐1), human telomerase reverse transcriptase, and survivin genes. Together, these results provide the first evidence that FHL2 contributes to glioma carcinogenesis. © 2008 Wiley‐Liss, Inc.