Purpose <p>Malignant meningiomas are characterized by high recurrence rates and limited therapeutic options beyond surgery and radiation. This study aimed to develop a novel nucleic acid-based therapeutic approach for malignant meningiomas and to evaluate its efficacy both in vitro and in vivo.</p> Methods <p>IOMM-Lee and HKBMM cell lines were used as models of malignant meningioma. Inhibitory effects of hemagglutinating virus of Japan envelope (HVJ-E) and microRNA-34a-5p (miR-34a-5p) were assessed using cell viability assays, apoptosis assays, RT-qPCR, and western blotting. Finally, the tumor suppressive effect of HVJ-E encapsulating miR-34a-5p was evaluated using a subcutaneous xenograft model in nude mice.</p> Result <p>HVJ-E significantly reduced viability of malignant meningioma cells. Furthermore, HVJ-E encapsulating miR-34a-5p demonstrated enhanced anti-tumor activity by inducing apoptosis through downregulation of survivin expression. This tumor-suppressive effect was also confirmed in a subcutaneous mouse model.</p> Conclusion <p>Our findings indicate that HVJ-E encapsulating miR-34a-5p effectively inhibits the growth of malignant meningioma cells both in vitro and in vivo. This novel combination therapy holds promise as a potential treatment strategy for malignant meningiomas.</p>