Background: Ribosomal protein s15a (RPS15A), a highly conserved cytoplasmic protein, promotes mRNA/ribosome interaction in translation. Recent evidence showed that RPS15A would be essential for tumor cell growth.Objective: The aim of this study was to investigate whether RPS15A has prognostic relevance in human glioblastoma.Material and methods: Levels of RPS15A expression were measured in glioblastoma and normal brain (NB) tissues samples. Stably decreased expression of RPS15A was established by the pLVTHM-GFP lentiviral RNAi expression system. Molecular mechanisms and the effect of RPS15A on cell growth and migration were investigated using MTT assay, wound healing assay, transwell migration assay, Flow cytometry analysis, western blot assay, immunofluorescence double labeling and tumorigenesis in nude mice.Results: Here we report that RPS15A is specifically overexpressed in human glioblastoma tumor tissues, and RPS15A knockdown inhibits proliferation and migration of glioblastoma cells in vitro. Lentivirus, transduced with shRPS15A, lead to depression of phosphorylated AKT, cell cycle arrest in G0/G1 phase in U87 cells, and also reduce expression of cell cycle regulation protein CDK4 while enhancing expression of p18INK4C. Furthermore, the growth of glioblastoma cell-transplanted tumors in nude mice is inhibited by transduction with Lv-shRPS15A.Conclusion: Our findings indicate that RPS15A promotes cell proliferation and migration in glioblastoma for the first time. RPS15A might play a distinct role in glioblastoma and serve as a potential target for therapy. Background: Ribosomal protein s15a (RPS15A), a highly conserved cytoplasmic protein, promotes mRNA/ribosome interaction in translation. Recent evidence showed that RPS15A would be essential for tumor cell growth. Objective: The aim of this study was to investigate whether RPS15A has prognostic relevance in human glioblastoma. Material and methods: Levels of RPS15A expression were measured in glioblastoma and normal brain (NB) tissues samples. Stably decreased expression of RPS15A was established by the pLVTHM-GFP lentiviral RNAi expression system. Molecular mechanisms and the effect of RPS15A on cell growth and migration were investigated using MTT assay, wound healing assay, transwell migration assay, Flow cytometry analysis, western blot assay, immunofluorescence double labeling and tumorigenesis in nude mice. Results: Here we report that RPS15A is specifically overexpressed in human glioblastoma tumor tissues, and RPS15A knockdown inhibits proliferation and migration of glioblastoma cells in vitro. Lentivirus, transduced with shRPS15A, lead to depression of phosphorylated AKT, cell cycle arrest in G0/G1 phase in U87 cells, and also reduce expression of cell cycle regulation protein CDK4 while enhancing expression of p18INK4C. Furthermore, the growth of glioblastoma cell-transplanted tumors in nude mice is inhibited by transduction with Lv-shRPS15A. Conclusion: Our findings indicate that RPS15A promotes cell proliferation and migration in glioblastoma for the first time. RPS15A might play a distinct role in glioblastoma and serve as a potential target for therapy.