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Background: This study was designed and conducted to determine the status of depression literacy (D-Lit) and its relationship with the quality of life across the Iranian population. Methods: This cross-sectional study was conducted in 2020 among 1382 participating from the general population in Gonabad, Iran. Participants were selected and recruited using a multistage sampling method. Data were collected using three sets of questionnaires (demographic section, D-Lit scale, and quality of life questionnaire). Data were analyzed by SPSS software version 24 and using independent samples t- test, Chi-square test, One-way ANOVA, and Pearson correlation. Results: Based on the results, the mean (± standard deviation) of D-Lit and quality of life were 44.14 (± 4.69) and 35.81 (± 5.17), respectively. Based on the results of Pearson correlation coefficient, there was a significant positive correlation between D-Lit and quality of life (r = 0.104, p < 0.001). D-Lit was significantly higher in those who reported having consulted with a psychiatrist compared with those who did not (p < 0.001). Participants with a family history of mental illness and those whose family members were referred to a psychologist for psychological issues had significantly higher levels of D-Lit than others (p < 0.001). Conclusion: Based on the results of this study, some D-Lit projects should be improved. Also, the results revealed that D-Lit is a potential factor that can affect people's mental health status and enhance their quality of life. Therefore, it is necessary to develop appropriate educational programs to enhance D-Lit in the community and ultimately improve the quality of life in the community by reducing mental illness. [ABSTRACT FROM AUTHOR]