The aim of this study was to explore the synergistic effect of signal transducer and activator of transcription 3 (STAT3)‑targeted small interfering (si)RNA and AZD0530 against glioblastoma in vitro and in vivo. Glioblastoma cell lines U87 and U251 were divided into four groups and treated with control, LV‑STAT3 siRNA, AZD0530, and combined LV‑STAT3 siRNA with AZD0530, respectively. The proliferation and apoptotic capacity of glioblastoma cells was assessed by Cell Counting Kit‑8 and double staining flow cytometry assays, respectively. Additionally, the potential effect of LV‑STAT3 siRNA and AZD0530 on glioblastoma was evaluated in vivo. Images were captured of the tumor formation in mice every week. Following three weeks of treatment, NMR scan and immunohistochemistry were performed. The treatment of combined LV‑STAT3 siRNA and AZD0530 was more effective in inhibiting proliferation and inducing apoptosisof glioblastoma cells in comparison with the treatment of either LV‑STAT3 siRNA or AZD0530 alone. Although LV‑STAT3 siRNA or AZD0530 treatment alone suppressed tumor growth in mice, the combined treatment had a more significant effect than the treatment of LV‑STAT3 siRNA or AZD0530 alone. According to the results of both in vitro and in vivo assays, a combined therapy of LV‑STAT3 siRNA with AZD0530 could enhance therapeutic effects on glioblastoma, supporting the idea that the combination of LV‑STAT3 siRNA and AZD0530 could serve as a novel and effective strategy to combat glioblastoma.