OBJECTIVES: To investigate the rates of depressive symptoms in college students, explore the relationship between urinary phthalate metabolites and depressive symptoms and their gender differences, and further explore the moderating role of insomnia in this association. METHODS: A total of 1 179 college students were recruited from 2 universities in Hefei and Shangrao cities from April to May 2019. The depressive symptoms and insomnia of college students were investigated by the Patient Health Questionnaire 9 and Insomnia Severity Index. The high-performance liquid chromatography-tandem mass spectrometry was adapted to determine the concentration of urinary phthalate metabolites. The generalized linear model was used to analyze the relationship of phthalate metabolites with depressive symptoms. Moderating analysis was used to examine whether insomnia moderated the relationship of phthalate metabolites with depressive symptoms. RESULTS: The rates of mild depression, and moderate depression and above in college students were 31.9% and 9.2%, respectively. The phthalate metabolites exhibited a median and mean concentration spanning from 2.98 ∼ 156.55 ng/mL and 6.12 ∼ 205.53 ng/mL. The generalized linear model results showed that monobutyl phthalate (MBP) (β = 1.160, 95%CI: 0.423 ∼ 1.896) and low molecular weight phthalate (LMWP) (β = 1.230, 95%CI: 0.348 ∼ 2.113) were positively correlated with depressive symptoms, and MBP (β = 1.320, 95%CI: 0.453 ∼ 2.187) and LMWP (β = 1.396, 95%CI: 0.351 ∼ 2.440) were positively correlated with depressive symptoms only in female college students after stratified by gender. Furthermore, insomnia has a positive moderating role between MBP, LMWP, and depressive symptoms and has a sex-based difference. CONCLUSIONS: This study suggests that there is a positive association of phthalate metabolites with depressive symptoms among Chinese college students, as well as insomnia plays a positive moderating role in this association.