Minimal hepatic encephalopathy (MHE) is characterized by a series of cognitive impairments. Thalamus is a critical pathological node of MHE. Thus, we applied probabilistic tractography to investigate the thalamic fiber pathway alterations in MHE, for the first time. The thalamic structural connection was disturbed in MHE patients (reflected by decreased CS/FA and increased MD/AD/RD). Abnormal thalamic connection primarily involved prefrontal cortex, sensorimotor cortex, parietal cortex, medial temporal cortex and hippocampus, and striatum. Thalamic connectivity abnormalities deteriorated with disease progression and correlated with patients’ impaired neuropsychological performance. The disturbed thalamic connectivity can serve as biomarker for diagnosis of MHE.