Abstract: Objective To know the quality of life (QOL) and it's influencing factors among patients infected with HIV with CD4+T lymphocyte counts (CD4 counts) ≤350/mm3 in Zhuhai City, so as to provide targeted interventions for HIV/AIDS. Methods Patients infected with HIV, whose CD4 counts were below 350/mm3 and who were followed up by Foshan Municipal Center for Disease Control and Prevention or medical institutions in Foshan from October 2013 to March 2014, were investigated by using WHO QOL HIV–BREF. Data of the patients including basic demographic information and related influencing factors were obtained from the "Information management system for the prevention and control of HIV/AIDS". Influencing factors of quality of life were analyzed by using multiple linear regression analysis method. Results A total of 179 cases were investigated. The average age was (39.56 ±11.65) years. Among all the cases, 72.07% were males; 33.52% were aged 30-39 years; 51.40% had educational background of junior high school; 51.40% were married; 80.45% were on the job; 50.28% were HIV-infected and 49.72% were patients with AIDS; 64.25% were not residents registered in the city. Heterosexual contact was the main route of HIV transmission (63.69%). The average scores of the cases were lower than those of the general population in psychological domain（13.17±2.72), independence domain（14.12±2.75）, and social relations domain（12.94±2.53）（P<0.01 for all）, but higher in spiritual pillar / religious faith domain (14.29±3.06)（P<0.01）. In multiple linear regression analysis, the related factors affecting the QOL were gender, education, local household registration, route of infection, receiving treatment of opportunistic infections, advertising materials,receiving highly active antiretroviral therapy, and access to condom use (P<0.05 or P<0.01). Especially the scores for HIV/AIDS patients infected through blood transfusion were lower in physical domain,independence domain and spiritual pillar/religious faith domain (partial regression coefficient:-4.67,-4.00,-7.24).Conclusion The QOL of HIV/AIDS patients with CD4 counts ≤350 /mm3 was lower than that of the general population and influenced by many factors. Relevant measures for corresponding domians should be formulated to improve the QOL of persons living with HIV/AIDS.