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Background: This paper investigates the relationship between psychological health and quality of life (QOL) of people affected by leprosy (PAL) living in a community in Guangdong province, China.Methods: A population-based cross-sectional survey was conducted from April to October 2016 in Guangdong province, China. The 12-item general health questionnaire (GHQ12) and World Health Organization Quality of life-BREF (WHOQOL-BREF) were used to evaluate the psychological health and QOL of the participants. PAL recruited for this study included those who were (1) registered in LEPMIS by the end of 2015 and living in the community, (2) able to be contacted by investigators, and (3) willing to provide informed written consent for enrolling in the study. Proportions, medians, and ratios were used to describe the demographics of the participants and χ2 test was used to compare groups with different psychological health states. Pearson's correlation coefficient and logistic regression analyses were used to assess the relationship between GHQ12 and QOL score.Results: A total of 7230 PAL (5527 males and 1701 females, average age 67.3 ± 13.1 years) living in the community participated in the study. The participants averaged 1.7 ± 2.7 points on the GHQ12. Of these, 23.5% had scores meeting a psychological disorder (≥3 points). The scores for the physical, psychological, and social relationships, and environment dimensions of QOL were 17.2 ± 2.4, 20.6 ± 2.7, 9.7 ± 1.7, and 24.6 ± 4.0, respectively. Gender, age, employment, profession, and the four dimensions of QOL were independent factors associated with psychological health of PAL.Conclusion: In addition to focusing on the factors associated with poor QOL and psychological health amongst PAL, there is an urgent need for stigma reduction, rehabilitation programs and social integration. This may be achieved by engaging community members together with PAL to design a locally tailored intervention program. [ABSTRACT FROM AUTHOR]