Abstractβ-Elemene is commonly used as an anti-cancer agent in different types of cancers and its effects on glioblastoma have been studied through different pathways. However, its effect through ring finger protein 135 (RNF135, OMIM 611358) (RNF135), which is upregulated in glioblastomas, has not yet been explored. The current study is focused on the effects of β-elemene on human glioblastoma cell lines U251, U118, A172 and U87 through RNF13 5. A cell counting kit-8 assay and wound healing assay have been utilized to test the proliferation and migration of the cells. Western blot and quantitative real-time-polymerase chain reaction (qRT-PCR) were used to evaluate the level of expression of RNF135. A model of nude mice was used to explore progression of the tumor in vivo. It was observed that increasing treatment time or dose of β-elemene remarkably decreased viability of the cells. The cells that were treated with β-elemene had a much lower speed of moving toward the gap in comparison to untreated cell lines. β-Elemene-treated cells showed a much lower level of expression of RNF135 mRNA than control groups (p <0.05) and the levels of RNF135 protein were lower in the cells treated with β-elemene than in control groups (p <0.05). Moreover, tumor progression in subcutaneous xenograft nude mice was delayed with the injection of β-elemene. Altogether, our findings suggest that β-elemene inhibits proliferation, migration and tumorigenicity of human glioblastoma cells through suppressing RNF135.