Introduction: Aging is one of the risk factors for intracranial aneurysm rupture. Aging causes various changes in cellular homeostasis, including cellular senescence. Cellular senescence is defined as a state of irreversible cellular growth arrest. Senescence cells secrete pro-inflammatory senescence-associated secretory phenotypes (SASPs). SASPs affect surrounding cells and contribute to a vicious cycle of senescence and induce inflammation. Recent studies strongly suggest that inflammation promotes aneurysm rupture. Therefore, the accumulation of senescence cells may induce aneurysm rupture due to pro-inflammatory effects of SASPs. We hypothesized that the elimination of senescence cells reduces the aneurysm rupture. To test our hypothesis we used p16-3MR mice. P16-3MR mouse is a transgenic mouse model, in which senescence cells can be eliminated by treatment of ganciclovir (GCV). In previous reports, the elimination of senescence cells by GCV in p16-3MR mice improved senescence-related diseases. In this study, we tested whether the elimination of senescence cells by GCV in p16-3MR mice reduces the intracranial aneurysm rupture rate. Methods: We induced intracranial aneurysms by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid in mice. We compared the vehicle to GCV group in p16-3MR aged male mice (10-15 months, vehicle vs GCV: 9 vs 6). We started GCV treatment the same day after aneurysm induction. Aneurysm rupture rate was used as the primary endpoint. Results: There was no statistical difference in the formation rate of aneurysms between the vehicle and the GCV group. However, the aneurysmal rupture rate was significantly lower in the senescence cell-depleted mice (P < 0.05). Additionally, the symptom-free curve (Kaplan-Meier analysis curve) showed a significant reduction of aneurysm rupture in the GCV-treated group (P < 0.05). Conclusions: The elimination of senescence cells reduced the aneurysm rupture rate in a mouse model of the aneurysm. Our results suggest that the accumulation of senescence cells induces aneurysm rupture. Therefore, the pharmacological prevention of the accumulation of senescence cells may be a new therapeutic target in aneurysm rupture.