A generally used chemotherapeutic drug for glioma, a frequently diagnosed brain tumour, is temozolomide (TMZ). Our study investigated the activity of FBXL7 and miR‐152‐5p in glioma. Levels of microRNA‐152‐5p (miR‐152‐5p) and the transcript and protein of FBXL7 were assessed by real‐time PCR and Western blotting, respectively. The migratory and invasive properties of cells were measured by Transwell migration and invasion assay and their viability were examined using CCK‐8 assay. Further, the putative interaction between FBXL7 and miR‐152‐5p were analysed bioinformatically and by luciferase assay. The activities of FBXL7, TMZ and miR‐152‐5p were analysed in vivo singly or in combination, on mouse xenografts, in glioma tumorigenesis. The expression of FBXL7 in glioma tissue is significantly up‐regulated, which is related to the poor prognosis and the grade of glioma. TMZ‐induced cytotoxicity, proliferation, migration and invasion in glioma cells were impeded by the knock‐down of FBXL7 or overexpressed miR‐152‐5p. Furthermore, the expression of miR‐152‐5p reduced remarkably in glioma cells and it exerted its activity through targeted FBXL7. Overexpression of miR‐152‐5p and knock‐down of FBXL7 in glioma xenograft models enhanced TMZ‐mediated anti‐tumour effect and impeded tumour growth. Thus, the miR‐152‐5p suppressed the progression of glioma and associated tumorigenesis, targeted FBXL7 and increased the effect of TMZ‐induced cytotoxicity in glioma cells, further enhancing our knowledge of FBXL7 activity in glioma.