OBJECTIVE To investigate the quality of life and its related factors among HIV/AIDS patients from HIV serodiscordant couples in Zhoukou city of Henan province. METHODS During January to May in 2015, by the convenience sample, World Health Organization Quality of Life Questionnaire for Brief Version (WHOQOL-BREF) (Chinese version) and a self-edited questionnaire were used to investigate 1 251 HIV/AIDS patients who were confirmed with HIV positive by local CDC, registered in"HIV serodiscordant family" and agreed to participate in a face-to-face interview with above 18 year-old based on the local CDC , township hospitals and village clinics of 9 counties and 1 district of Zhoukou city, excluding the HIV/AIDS patients who were in divorce, death by one side, unknowing about his HIV status, with mental illness and disturbance of consciousness, incorrectly understanding the content of the questionnaire, and reluctant to participate in this study. The scores of quality of life of physical, psychological, social relations, and environmental domain were calculated. The related factors of the scores of different domains were analyzed by Multiple Two Classification Unconditioned Logistic Regression. RESULTS The scores of investigation objects in the physical, psychological, social relations, and environmental domain were 12.00± 2.02, 12.07 ± 2.07, 11.87 ± 1.99, and 11.09 ± 1.84, respectively. The multiple Unconditioned Logistic Regression analysis indicated that age <40 years, on ART and no other sickness in last two weeks were beneficial factors associated with physical domain with OR (95%CI): 0.61 (0.35-1.06), 0.52 (0.30-0.90), and 1.66 (1.09-2.52), respectively. The possibility of no poverty and no other sickness in last two weeks increased to 0.15(0.09-0.26) and 1.57(1.06-2.33) times of those who was in poverty and with other sickness in last two weeks in physical domain. The possibility of participants who were below 40 years old and with children increased to 0.58 (0.34-0.98) and 0.37 (0.23-0.57) times of who were above 40 years old and without children in psychological domain. The factors of with AIDS related symptoms, no children and with other sickness in last two week were found to be significantly associated with environmental domain with OR (95%CI): 0.65 (0.48-0.88), 0.66 (0.51-0.85), and 0.65 (0.51-0.84), respectively . CONCLUSIONS The scores of every domain of quality of life in HIV serodiscordant couples of Zhoukou city were good. Age, whether having AIDS related symptoms, whether to accept ART , children, status of poverty, and whether suffering from other diseases in last two weeks were the main factors associated with the quality of life.