Abstract Background Patient-specific approach design, comprehensive evaluation on perioperative data, and follow-up of postoperative life quality (KPS) were carried out to evaluate the application of VR technology of Dextroscope in procedures of patients with skull base tumors. Methods Eighty-four patients with skull base tumors involved in this research were randomized into 2 groups (test group and control group), each with 42 patients. Before operation, image data such as MR, MRA, or CTA of head were collected and imported into the Dextroscope workstation. The detailed preoperative plans were made in the test group, but no Dextroscope plans in control group. The resection rate of tumors, preoperative evaluation including the duration of operation, total blood loss, the postoperative LOS, the number of cases with cerebrovascular injury complications in operation, and postoperative KPS of patients on discharge and the sixth month follow-up in the 2 groups were recorded and compared. Results The total resection rate of tumors was 83.33% in test group and 71.42% in the control group ( P > .05). The total resection rate of meningioma was 86.67% in test group and 76.47% in control group. The total resection rates of trigeminal Schwannoma in the 2 groups were all 100% ( P > .05). The duration of operation and the postoperative LOS of each patient were 5.25 ± 0.64 hours and 8.50 ± 1.10 days in the test group and 7.36 ± 0.87 hours and 12.50 ± 1.52 days in the control group, respectively ( P < .05). Total blood loss of each patient was 456.75 ± 55.76 mL in the test group and 523.85 ± 66.78 mL in the control group ( P > 05). There were 3 cases with complications of cerebral vessels injury in the test group and 7 cases in the control group ( P < .05). During follow-up, KPS of patients in the test group on discharge (85.75 ± 9.68) was significantly superior to that in the control group (81.66 ± 9.24; P < .05). The KPS of patients on the sixth-month follow-up in the test group was 92.35 ± 9.95, which was significantly superior to that in the control group (85.6 ± 9.34; P < .05). Karnofsky performance scores of patients in the test group improved significantly from discharge to the sixth month after procedure ( P < .05), whereas there were adverse results in the test group ( P < .05). The 2 cases with CSF leakage were cured completely. Conclusion The preoperative plans with VR technology in patients with skull base tumor or CSF leakage operations can help certain the diagnosis, individually locate the position of skull base lesions, and design patient-specific approach, which also facilitate to shorten operation duration and the postoperative LOS, reduce total blood loss and injury of vessels in operation, and improve the postoperative KPS.