Objective: Patients with hypochondriasis hold unexplainable beliefs and a fear of having a lethal disease, with poor compliances and treatment response to psychotropic drugs. Although several studies have demonstrated that patients with hypochondriasis demonstrate abnormalities in brain structure and function, gray matter volume and functional connectivity in hypochondriasis still remain unclear.Methods: The present study collected T1-weighted and resting-state functional magnetic resonance images from 21 hypochondriasis patients and 22 well-matched healthy controls. We first analyzed the difference in the GMV between the (...) two groups. We then used the regions showing a difference in GMV between two groups as seeds to perform functional connectivity analysis. Finally, a support vector machine was applied to the imaging data to distinguish hypochondriasis patients from HCs.Results: Compared with the HCs, the hypochondriasis group showed decreased GMV in the left precuneus, and increased GMV in the left medial frontal gyrus. FC analyses revealed decreased FC between the left medial frontal gyrus and cuneus, and between the left precuneus and cuneus. A combination of both GMV and FC in the left precuneus, medial frontal gyrus, and cuneus was able to discriminate the hypochondriasis patients from HCs with a sensitivity of 0.98, specificity of 0.93, and accuracy of 0.95.Conclusion: Our study suggests that smaller left precuneus volumes and decreased FC between the left precuneus and cuneus seem to play an important role of hypochondriasis. Future studies are needed to confirm whether this finding is generalizable to patients with hypochondriasis. (shrink)