ObjectiveFamily conflict is an important risk factor for major depressive disorder (MDD) and is associated with structural alterations in the brain. However, it is unclear whether structural alterations associated with family conflict would contribute to depression. This study aims to investigate the neuroimaging characteristics that connect family conflict with depression. MethodsThis study included 54 healthy controls and 53 antidepressant-free patients with MDD. Both groups completed the Beck Depression Inventory-II, the simplified Chinese version of the Family Environment Scale, and the Childhood Trauma Questionnaire. Structural Magnetic Resonance Imaging data was collected to measure cortical thickness and regional gray matter volumes. ResultsFamily conflict has a significant effect on depression diagnosis. Higher levels of family conflict were positively associated with symptoms of sadness, guilty feelings, and punishment feelings in patients, as well as with cortical thickness in the right inferior-parietal cluster and the volumes of the left globus pallidus in all participants. In the patient group, cortical thickness in the right inferior-parietal cluster and volume of the left globus pallidus were negatively related to symptoms of sadness and guilty feelings, respectively. The structural alteration in the right inferior-parietal cluster mediated the relationship of family conflict and sadness, whereas changes in the globus pallidus mediated the associations between family conflict and both depression and guilty feelings in patients. ConclusionFindings revealed the relationships between family conflict and depression, including both depression diagnosis and specific symptoms. Cortical thickness in the right inferior-parietal cortex and the volume of the left globus pallidus played mediating roles in these relationships, indicating the important contributions of these brain regions to the effect of family conflict on depression.