Our study aimed at comparing the diagnostic value of F-18-NaF positron emission tomography-computed tomography (PET/CT) and F-18-fluorodeoxyglucose (FDG) PET/CT for detection of skull-base invasion and osseous metastases in patients with nasopharyngcal carcinoma (NPC). Our study retrospectively analyzed 45 patients with pathologically proven NPC. They all underwent both F-18-NaF PET/CT and F-18-FDG PET/CT within a 7-day interval. Bone metastases were confirmed by follow-up using PET/Cr, enhance-contrast computed tomography (CT), and magnetic resonance image (MRI). These two examinations were compared using per-patient-based analysis and per-lesion-based analysis. F-18-NaF PET/CT detected 27 patients with skullbase invasion, whereas F-18-FDG PET/CT detected 17 patients. F-18-NaF PET/CT and F-18-FDG PET/CT differed significantly in diagnosing skull-base invasion (p = 0.02) and sensitivity (p = 0.008). The sensitivity, specificity, and agreement rate of F-18-NaF PET/CT for detecting bone metastatic lesions were 98.3%, 65.7%, and 92.9%, respectively; these values were 42.9%, 97.1%, and 51.9%, respectively, for F-18-FDG PET/CT. F-18-NaF PET/CT and F-18-FDG PET/CT differed significantly in the number of osseous metastases detected (t = 2.45, p = 0.18) sensitivity (p<0.0001) and specificity (p = 0.003). In patients with nasopharyngeal carcinoma, F-18-NaF PET/CT assessed invasion of the skull base better and detected more osseous metastases than F-18-FDG PET/CT.