This study was designed to explore the function of lncRNA MAFG‑AS1/miR‑642a‑5p/Notch1 in glioblastoma (GBM) cells under radiation. GBM cells (M059K and M059J) were transfected or/and irradiated. Western blotting was used to detect Notch1 protein and its downstream Hes1 protein. Cell Counting Kit-8 assay and flow cytometry were applied for viability and apoptosis tests, respectively. Luciferase reporter plasmids and Ago2 antibody were used to verify the predicted binding of miR‑642a‑5p to MAFG‑AS1 or Notch1 mRNA. Notch1 and MAFG‑AS1 were highly expressed and miR‑642a‑5p was lowly expressed in radioresistant M059K cells. Knockdown of Notch1 inhibited radioresistance and promoted apoptosis in M059K cells. MAFG‑AS1 competed with Notch1 mRNA for binding of miR‑642a‑5p and therefore promoted the expression of Notch1. Overexpression of miR‑642a‑5p or silencing of MAFG‑AS1 inhibited the radioresistance of M059K cells. Knockdown of Notch1 or overexpression of miR‑642a‑5p reduced viability and increased apoptosis in irradiated M059J cells overexpressing MAFG‑AS1. MAFG‑AS1 reduces the radiosensitivity of GBM cells via miR‑642a‑5p/Notch1 axis.