ObjectiveAlcohol use disorder (AUD) is the second most prevalent mental disorder and might be related to depression. Major vault protein (MVP) is a cytoplasmic protein related to vesicle transport. The present study aimed to investigate the interaction between a genetic variant (MVP rs4788186) and depression in adult male Han Chinese with AUD during withdrawal.MethodsAll participants (N = 435) were diagnosed with AUD. Alcohol dependence level was measured using the Michigan Alcoholism Screening Test, and depression was measured using the self-rating depression scale. Genomic DNA was extracted from peripheral blood and genotyped.ResultsHierarchical regression analysis identified an interaction between MVP rs4788186 and alcohol dependence level for depression (β = −0.17, p