Mitogen-activated and stress-activated protein kinase 1 (MSK1), which belongs to the subfamily of MAPK-activated protein kinase, plays an important role in cell proliferation and neoplastic transformation. It has been recently reported that MSK1 overexpression was closely related to the progression of some tumors such as colorectal cancer. However, the clinical significance of MSK1 in glioma has not been addressed. To investigate the potential role of MSK1 in glioma, we first examined the expression pattern of MSK1 in glioma tissues and normal brain tissues using quantitative RT-PCR, and the results showing that MSK1 expression was significantly elevated in glioma tissues compared with normal brain tissues. The clinical relevance of MSK1 expression level was then analyzed, and we found that high expression of MSK1 was closely related to the larger tumor size and advanced WHO grade. Univariate and multivariate analyses revealed that glioma patients with higher expression of MSK1 had poorer overall survival, and MSK1 was identified as an independent unfavorable prognosis factor. In addition, the effects of MSK1 on glioma cells were tested through cellular experiments, and we demonstrated that MSK1 can promote proliferation and invasion capacities of tumor cells. In conclusion, patients with glioma with higher MSK1 expression were more predisposed to poorer clinical outcomes and unfavorable prognosis, indicating the potential role of MSK1 as a novel clinical biomarker and therapeutic target.