Background DICER1 can generate mature microRNAs,which are aberrant expression in major depressive disorder (MDD) and approved to play a vital role in the pathogenesis of MDD.The purpose of this study is to explore whether rs10144436 polymorphism in DICER1 gene is associated with MDD risk.Methods We first genotyped the single nucleotide polymorphisms (SNPs) of DICER1 rs10144436 in stage Ⅰ,which included 221 paired MDD patients and controls,and then validated the results in stage Ⅱ,which recruited another 305 paired MDD patients and controls.In addition,we examined the expression of DICER1 in blood samples of 100 paired MDD patients and controls.Results In stage Ⅰ,we found that rs10144436 polymorphism was significantly associated with increased MDD risk (AA vs CC: adjusted OR =2.32,95%CI =1.28-4.17,P =0.005;additive model: adjusted OR =1.52,95%CI =1.03-2.25,P =0.037).Then the rs10144436 SNP was significantly replicated in stage Ⅱ.When pooled the two stages together,the results indicated that the A allele ofrs10144436 was associated with a 75% increased risk of MDD (additive model: OR =1.75,95%CI =1.37-2.24,P < 0.001).In addition,stratification analysis showed that MDD patients with CA or AA genotype had higher recurrence risk compare with patients carrying CC genotype (CA vs CC: adjusted OR =1.80,95%CI =1.18-2.74,P =0.007;AA vs CC: adjusted OR =1.59,95%CI =1.11-2.27,P =0.012).Furthermore,the expression level of DICER1 in MDD patients was significantly lower than that in controls (P <0.001) and the genotype-phenotype analysis suggested that patients carrying CA or AA genotype had lower expression level of DICER1 than those with the CC genotype (P < 0.05).Conclusions Our findings provided evidence that the rs10144436 polymorphism was associated with the development of MDD by regulating the DICER1 expression level.