PurposeVon Hippel-Lindau (VHL) syndrome is a rare autosomal dominant diseases involved multiple organs. This paper aims to explore the clinical and imaging features of VHL syndrome for the improvement of early diagnosis and treatment of this disease.Materials and Methods The clinical and imaging data, as well as their history of 5 patients with VHL syndrome were retrospectively studied. Follow-up was performed and the related literature was also reviewed.Results Among the 5 patients, 4 were found with angioreticulomas. One out of four patients simultaneously suffered from multiple angioreticulomas in brainstem, and another one had multiple cervical cord angioreticulomas. The typical MRI showed multiple cystic and solid mass with mixed intense signals, and the enhanced MRI displayed obvious enhancement in the solid part of the mass. Three patients were diagnosed with renal clear cell carcinomas. The typical CT scan showed equidensity or slightly low density signals, and the enhanced CT scan noted heterogeneous enhancement. Besides, bilateral epididymis cystadenoma occurred in one case. The ultrasonography presented heterogeneous echo and rich blood vessels. The follow-ups had been conducted till January 2015. According to the Glasgow outcome scale, three patients were in good conditions, while the other two died from renal clear cell carcinomas.Conclusion Patients with VHL syndrome usually have an unsatisfactory prognosis and most may die from renal carcinoma. Genetic test and investigation of family history should be performed as early as possible on patients with highly suspected or confirmed VHL Early treatment, life-long follow-up and periodic imaging examinations may be helpful in the prognosis.