In total maxillectomy, the entire upper jaw including the tumor is removed en bloc from the facial skeleton. An intraoperative computed tomographic guidance system (ICTGS) can improve orientation during surgical procedures. However, its efficacy in head and neck surgery remains controversial. This study evaluated the use of an ICTGS in total maxillectomy. Five patients with maxillary sinus neoplasms underwent surgery using a StealthStation ICTGS. The headset was used for anatomic registration during the preoperative CT scan and surgical procedure. The average accuracy was 0.95 mm. The ICTGS provided satisfactory accuracy until the end of resection in all cases, and helped the surgeon to confirm the anatomical location and decide upon the extent of removal in real time. It was particularly useful when the zygoma, maxillary frontal process, orbital floor, and pterygoid process were divided. All patients remained alive and disease free during short-term follow-up. The ICTGS played a supplementary role in total maxillectomy, helping the surgeon to recognize target points accurately in real time, to determine the minimum accurate bone-resection line, and to use the most direct route to reach the lesion. It could also reduce the extent of the skin incision and removal, thus maintaining oncological safety.