Objective To investigate the association between vesicular monoamine transporter 2 (VMAT2) polymorphisms, rs363371 and rs363324, and depression in the Han Chinese population with Parkinson's disease (PD).Methods A total of 102 Han Chinese patients with PD were enrolled and divided into PD with depression group and PD without depression group according to the 17-item Hamilton Depression Rating Scale. The two single nucleotide polymorphisms (SNPs) of VMAT2, rs363371 and rs363324, were genotyped using ligase detection reaction. Binary logistic regression was used to analyze the risk factors for depression in PD.Results The AA genotype at rs363371 reduced the risk of depression in PD[odds ratio (OR)=0.22, 95% confidence interval (CI):0.07-0.75, P=0.015]. The high score for UP3 increased the risk of depression in PD (OR=1.08, 95%CI:1.02-1.15, P=0.009). Long duration of PD increased the risk of depression in PD (OR=1.15, 95%CI:1.01-1.31, P=0.038). The VMAT2 SNP rs363324 did not increase the risk of depression in PD.Conclusions The AA genotype at rs363371 reduces the risk of depression in the Han Chinese population with PD.