The patient, a 30-year-old female, presented to the clinic with a 2-month history of nasal congestion and rhinorrhea. Local CT and MRI reports suggested that a mass was seen in the anterior part of the septal and pterygoid sinuses and in the area of the olfactory fissure near the skull base, with significant image enhancement. Local hospital biopsy showed a medium to low differentiated squamous carcinoma. After admission, a transnasal endoscopic resection of the lesion in the skull base region of the sinuses was performed. Multiple intraoperative pathological examinations revealed extensive tumor invasion, which was found in the mucosa, cartilage, and bone in the skull base region. The tumor was completely removed endoscopically, along with part of the dura mater. Reconstruction of the skull base was then performed. The patient returned to the ward safely after the operation. The patient recovered well after surgery. Adjuvant chemotherapy and radiotherapy were continued. The prognosis for this type of squamous cell carcinoma of the septal sinus and skull base is generally poor. The overall 5-year survival rate is around 50%. The proximity of the disease to the skull and the orbital optic nerve makes it difficult to perform complete resection of the tumor and to perform tumor detection at the peripheral borders (especially close to brain tissue, important cranial nerves, optic nerves, and internal carotid arteries), so microscopic tumor residuals are inevitable. Therefore, chemotherapy and radiotherapy must be administered according to the pathological status and the extent of the disease. Such patients are highly susceptible to occult metastases in the lymph nodes, although they are not detected prior to surgery.