Background: Depression is one of the most common mental illnesses that decrease quality of life. Medical students worldwide are increasingly affected by depression. This article focuses on depression in the preclinical medical students whose learning environment is different from medical students in clinical years. The aim of this study is to determine: (1) the prevalence of depression in Thai preclinical medical students; and (2) the factors associated with depression. This study will contribute to more specific and proper interventions concerning depression in Thai preclinical medical students.Methods: A cross-sectional study was performed at the Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. The Patient Health Questionnaire-9 (PHQ-9), Thai version was applied to explore prevalence of depression. The selected associated factors, including interpersonal relationships, mindfulness, and self-esteem were determined using peer-relationship questionnaire, family-relationship questionnaire, Thai version of the Philadelphia Mindfulness Scale (PHLMS) and Thai version of Rosenberg’s self-esteem scale respectively. Analysis was done using risk estimation by applying a contingency table and univariate logistic regression.Results: Among 275 preclinical medical students participating in this study, 71 (25.8%, 95%CI[ 0.207,0.310]) had a PHQ-9 score of 9 or more. Four associated factors were significantly correlated with lower PHQ-9 scores. These protective factors included (1) a personal counselor or peer support; (2) a good family relationship; (3) a higher score in the Thai version of the Philadelphia Mindfulness Scale (PHLMS); and (4) autonomy in the medical student’s decision to study medicine.Conclusion: The prevalence of depression among Thai preclinical medical students was found to be higher than that of the general population (18.4%). Several factors were associated with a lower PHQ-9 score, including having a personal counselor or peer support, the participant’s own decision to study at medical school, having a good family relationship, and having mindful thoughts.