Background: Few studies have investigated the relative factors of thyroid dysfunction in major depressive disorder (MDD) patients with Metabolic syndrome (MetS). This study aimed to explore the prevalence and related factors associated with thyroid dysfunction in drug-naive (FEDN) MDD patients with MetS.Methods: 1718 FEDN MDD patients were recruited and their demographic data, clinical data were collected. Various biochemical indicators including fasting blood glucose (FBG), blood lipids and thyroid hormones were measured. The 17-item Hamilton Rating Scale for Depression (HAMD-17), 14-item Hamilton Anxiety Rating Scale (HAMA-14) and positive subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess clinical symptoms.Results: Among FEDN MDD patients, MetS was an independent risk factor for TSH abnormality (P < 0.001, Adjusted OR = 3.77, 95%CI: 2.82-5.05). In patients with MetS, those with TSH abnormality had significantly longer duration of illness, higher HAMD, HAMA, and PANSS positive subscale scores, higher levels of TC, LDL-C, blood glucose, pressure, lower levels of HDL-C, and a higher probability of suicide attempt (all P < 0.01).Conclusions: MetS is significantly associated with thyroid dysfunction in patients with FEDN MDD. Related factors for thyroid dysfunction include a number of clinical indicators and psychiatric symptoms.