Background: Patients with obstructive sleep apnea (OSA) are at high risk for rapid oxygen desaturation during anesthesia induction. Apneic oxygenation with high-flow nasal oxygen (HFNO) has proven effective in prolonging safe apnea time in various patient populations. However, evidence for the efficacy of HFNO in OSA patients remains limited. This study aimed to evaluate whether the use of HFNO during anesthesia induction in OSA patients prolongs safe apnea time. Methods: In this prospective randomized clinical trial, all participants underwent standardized pre-oxygenation and anesthesia induction. During the apneic period, oxygen was delivered either via HFNO at 60L/min (HFNO group) or with the nasal cannula left in place but disconnected from the oxygen source (control group, no supplemental oxygen). The primary outcome of this study was the time to peripheral oxygen desaturation (SpO(2) < 95%) during apneic oxygenation. Secondary outcomes included minimum SpO(2), re-oxygenation time, and tcCO(2) levels. Results: The HFNO group demonstrated a significantly prolonged safe apnea time compared to the Control group (18.1 [12.1,18.8] vs 4.2 [2.5,6.3] minutes; p <0.001). Additionally, minimum SpO(2) levels were higher, and re-oxygenation time was shorter in the HFNO group (p <0.001 for both). Kaplan-Meier survival analysis revealed a substantially reduced risk of desaturation in the HFNO group (hazard ratio: 0.071; 95% CI, 0.021-0.222; p <0.001). No serious adverse events were reported. Conclusion: In this randomized controlled trial, HFNO significantly prolongs safe apnea time and enhances oxygenation during anesthesia induction in OSA patients. These findings highlight the potential of HFNO to improve perioperative airway management and patient safety in this high-risk population.