Depression is a common mental disorder associated with sleep problems and the circadian clock genes may underlie the relationship between the two in clinical samples. However, little is known about whether poor sleep quality is associated with depressive symptom in healthy individuals and whether is mediated by specific single-nucleotide polymorphisms (SNPs).Using a cross-sectional design, 444 university staff members were randomly recruited in Beijing. We used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality, the Zung's Self-rating Depression Scale (SDS) to measure depressive symptom, and the Work Stress Scale to measure job stress. The CLOCK gene rs12649507 polymorphism was genotyped in 289 blood samples.There were positive inter-correlations between job stress, PSQI and SDS (almost ps  0.05). Interestingly, after controlling for job stress and covariates, the significant effect size of the SNP on the SDS mediated by the PSQI was 0.68 (95% CI [0.24, 1.35]).Some limitations included single professional background, cross-sectional study design, small sample size and potential confounding factors, which could be amended by future research.Non-clinical Chinese carrying CLOCK gene rs12649507 G-allele may lead to poor sleep quality and further depression symptoms.