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Background HIV/AIDS is an issue that seriously endangers public health. With the implementation of social support policies for people living with HIV/AIDS, although the mortality of them has decreased significantly, their survival is still a big concern. Objective To understand the quality of life and influencing factors in people living with HIV/AIDS in Henan rural areas. Methods By use of cluster sampling, we selected the persons living with HIV/AIDS treated by highly active antiretroviral therapy (HAART) who were managed by the local center for disease control and prevention in a rural area of Henan from June 3 to June 12, 2020. We collected their general data and laboratory test findings, and assessed their quality of life using the Chinese version of the WHOQOL-HIV BREF. We used multiple linear regression to identify the associated factors of quality of life. Results A total of 415 cases attended the questionnaire survey, and 400 of them (96.39%) who effectively completed the questionnaire were finally included for analysis. All the respondents were Han people, most of them were diagnosed over eight years, males, and aged over 50 years, and had a spouse, no stable income, low education level and CD4+ T lymphocytes greater than 500/μl with transmission mainly through blood, and over eight years of continuous HAART. The total score of quality of life of the respondents differed by sex, age, education level, marital status, income status, route of getting HIV infection, time of HIV diagnosis, and continuous treatment duration of HAART (P