Abstract: Objective To analyze the correlativity of depression with the dimensions of quality of life (QOL) of leprosy patients. Methods The center epidemiological studies of depression scale (CES-D) and world health organization quality of life questionnaire-brief version (WHOQOL-bref) were used to assess the depression and QOL of leprosy patients in Guangdong Province, and their correlativity was analyzed by the multiple linear regression analysis method. Results A total of 263 participants completed the survey, including 177 males (67.3%) and 86 females (32.7%). Among them, 131 participants (49.8%) presented depression symptoms, and these people got significant lower scores in all the dimensions of QOL than people without depression symptom(all P<0.05). The regression coefficients between depression and overall QOL, physical, psychological, social relationship and environment were -0.340, -0.322, -0.644, -0.424 and 0.244, respectively. All the regression coefficients got statistical significance (all P<0.05), except overall QOL. Conclusions High depression symptom rate has been found in leprosy patients in Guangdong Province, the QOL scores have significant correlations with CES-D score. Multilevel interventions should be taken to prevent the occurrence of depression among leprosy patients.