Beta-thalassemia minor is a common genetic blood disorder in Mediterranean countries such as Turkey. Additionally, depression is one of the most widespread mental disorders that affect people worldwide, and its prevalence is increasing with co-occurring medical conditions. The aim of this study was to determine whether the frequency of depression is elevated in subjects with beta-thalassemia minor. A total of 106 subjects were included in this study, of which 53 participants were diagnosed with beta-thalassemia minor. The other 53 participants were otherwise healthy. Hemoglobin electrophoresis and a complete blood count were performed in all subjects, and all participants were evaluated using the Hamilton Depression Rating Scale (HDRS). The HDRS scores of the subjects with beta-thalassemia minor were higher than those in the healthy subjects (p < 0.001). Additionally, the hemoglobin A2 levels were positively associated with the HDRS scores (p < 0.0001, r = 0.482). This study suggests a possible association between depression and beta-thalassemia minor, in which the risk of depression may be increased in subjects with this condition.