Objective: To explore the value of incorporated multimodal image fusion technology with computer-aided design of the skull base-infratemporal tumor treatment. Methods: A retrospective study was carried out to enroll seventeen patients with skull base-infratemporal tumors treated at Peking University Hospital of Stomatology from February 2011 to September 2018. Plain CT, enhanced CT and MRI data were imported into the iPlan 3.0 software (BrainLab navigation system), and the image fusion was performed for each patient preoperatively. Then the three-dimensional images of the tumor, vital vessels and craniofacial bones were reconstructed to prepare virtual operation design. We evaluated the application of multimodal image fusion technology that had been incorporated with computer-aided planning during the navigation-guided biopsy or surgery, through the analysis of the biopsy and operation data and re-gular follow-up postoperatively. Results: The mean age of 17 patients (7 males and 10 females) was 46 years. Primary tumors occurred in 11 cases, and recurrent tumors in 6 cases. The size of the 17 tumors ranged from 2.9 cm to 9 cm, and the mean size was 4.35 cm. There were 7 cases with skull base bone destruction and/or intracranial extension, and 10 cases with tumors adjacent to the skull base. High-quality multimodal fused images were obtained in all the 17 cases. The spatial-position relationships of the tumors, adjacent craniomaxillofacial bones and vital vessels labeled with different colors were displayed well on the generated fusion images. The multimodal image fusion technology that incorporated with computer-aided three-dimensional reconstruction and then applied in navigation-guided biopsy or surgery showed that, preoperative analysis and virtual operation design functioned with good results, especially in cases with small tumor size, recurrence or ill-defined borders in the skull base-infratemporal region. Operation was carried out in 16 cases after preoperative diagnosis and assessment, and 1 case was performed by navigation-guided biopsy only. The proportions of navigation-guided surgery and biopsy were 70.6% (12/17) and 17.6% (3/17) individually. The positive rate of pathologic diagnosis using navigation-guided biopsy was 100% (3/3). All the navigation-guided biopsies or operations were carried out successfully. Complications included 1 case of cerebrospinal fluid leak from a recurred meningioma patient postoperatively, and 1 case of facial paralysis resulting from parotid-gland deep lobe tumor. Most (14/15) tumors got complete removal with safe boundary through intra-operative navigation verification and post-operative imaging confirmation, except for one case of subtotal resection to avoid the injury of cavernous sinus. The pathological results of the tumors could be classified to mesenchymal (10), adenogenous (3), neurogenic (3) or epithelial (1) resources. The follow-up time ranged from 3 to 94 months, with the median follow-up time of 9 months. Conclusion:Taking full advantages of individualized multimodal images, could help analyze the three-dimensional spatial position relationship of tumors, vital vessels and craniofacial bones properly, and then complete the virtual operation design well. The incorporated multimodal image fusion technology with navigation technology may improve the accuracy and safety of core needle biopsy and surgical treatment of skull base-infratemporal tumors.