Background: Non-cardiac chest pain (NCCP) is a common patient complaint imposing great costs on the healthcare system. It is associated with psychological factors such as depression. The aim of the present study is determining depression predictors in NCCP patients. Methods: The participants of this cross-sectional study were 361 NCCP patients. Patients filled out questionnaires concerning their sociodemographic, lifestyle, and clinical factors (severity of pain, type D personality, somatization, cardiac anxiety, fear of body sensations, and depression). Results: Based on multiple ordinal logistic regression, lack of physical activity (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.09-2.87), sleep quality (OR, 2.98; 95% CI, 1.15-7.69), being a smoker (OR, 1.33; 95% CI, 2.41-4.03), present pain intensity (OR, 1.08; 95% CI, 1.05-1.11), type D personality (OR, 2.43; 95% CI, 1.47-4.03), and somatization (OR, 1.22; 95% CI, 1.15-1.3) were significant predictors of depression in NCCP patients. Additionally, multiple linear regression showed that being unmarried (β = 1.51, P = 0.008), lack of physical activity (β = 1.22, P = 0.015), sleep quality (β = 2.26, P = 0.022), present pain intensity (β = 0.07, P = 0.045), type D personality (β = 1.87, P < 0.001), somatization (β = 0.45, P < 0.001), and fear of bodily sensation (β = 0.04, P = 0.032) increased significantly depression scores in NCCP patients. Conclusions: Physicians should consider the predictors of depression in NCCP patients which can lead to receiving effective psychological consultations and reducing the costs and ineffectual referrals to medical centers.