Objective · To investigate the clinical value of 18F-flurodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) -guided percutaneous biopsy in peritoneal thickening of unknown origin. Methods · Ten cases of peritoneal thicken of unknown origin including 4 males and 6 females were analyzed. After 18F-FDG PET/CT examination, the peritoneal thickening regions with high 18F-FDG uptake were selected for the target areas. Percutaneous biopsy was operated under the guidance of the same PET/CT machine. Results · All lesions were successfully obtained by one-time puncture without serious complications, and histopathological diagnosis revealed that 7 cases were malignant, including 4 cases of peritoneal metastasis and 3 cases of lymphoma. The remaining cases were 1 case of pseudomyxoma, 1 case of tuberculosis and 1 case of inflammatory lesions. The accuracy of biopsy was 100%. Conclusion · 18F-FDG PET/CT-guided peritoneal percutaneous biopsy is a safe and effective method, and may play an important role in differential diagnosis and treatment management.