To investigate the effects of different ventilation strategies on intraocular pressure (IOP) and intracranial pressure in patients undergoing spinal surgery in the prone position under general anesthesia. Seventy-two patients undergoing prone spinal surgery under general anesthesia between November, 2022 and June, 2023 were equally randomized into two groups to receive routine ventilation (with Vt of 8mL/kg, Fr of 12-15/min, and etCO2 maintained at 35-40 mmHg) or small tidal volume hyperventilation (Vt of 6 mL/kg, Fr of18-20/min, and etCO2 maintained at 30-35 mmHg) during the surgery. IOP of both eyes (measured with a handheld tonometer), optic nerve sheath diameter (ONSD; measured at 3 mm behind the eyeball with bedside real-time ultrasound), circulatory and respiratory parameters of the patients were recorded before anesthesia (T0), immediately after anesthesia induction (T1), immediately after prone positioning (T2), at 2 h during operation (T3), immediately after supine positioning after surgery (T4) and 30 min after the operation (T5). Compared with those at T1, IOP and ONSD in both groups increased significantly at T3 and T4(P < 0.05). IOP was significantly lower in hyperventilation group than in routine ventilation group at T3 and T4(P < 0.05), and ONSD was significantly lower in hyperventilation group at T4(P < 0.05). IOP was positively correlated with the length of operative time (r=0.779, P < 0.001) and inversely with intraoperative etCO2 at T3(r=-0.248, P < 0.001) and T4(r=-0.251, P < 0.001).ONSD was correlated only with operation time (r=0.561, P < 0.05) and not with IOP (r=0.178, P>0.05 at T3; r=0.165, P>0.05 at T4). Small tidal volume hyperventilation can relieve the increase of IOP and ONSD during prone spinal surgery under general anesthesia.