Health-related quality of life (HRQOL) has become a concept commonly used in the related research. Using the World Health Organization Quality of Life Questionnaire for Brief Version (WHOQOL-BREF), this study evaluated the Quality of Life (QOL) of people living with HIV/AIDS (PLWHA) in Zhejiang province, China, and assessed the influences of demographic, laboratory and disease-related variables on QOL. This cross-sectional study was conducted among PLWHA aged ≥ 18 years in Taizhou municipality, Zhejiang province, China, between August 1 and October 31, 2014. A multiple linear regression model was used to analyze the influential factors. Of 403 subjects, 72.48% were male, 72.46% had received a high- school or above education, 94.79% were of Han ethnicity, and 65.51% were non farmers. The total score of QOL was 15.99±1.99. The scores of QOL in physiological, psychological, social relation, and environmental domains were 14.99 ±2.25, 14.25 ±2.12, 13.22 ±2.37, and 13.31 ±1.99 respectively. Except the total score of QOL and the score of environmental domain (p<0.05), the scores in other domains had no significant difference with the results of the national norm level. The multiple linear regression model identified the physical domain related factors to be age (β = -0.045), CD4 count (β = 0.002), and ART adherence(β = 1.231). And it also showed that psychological domain related factors included CD4 count (β = 0.002) and WHO clinical stage (β = -0.437); social domain related factors included WHO clinical stage (β = -0.704) and ART adherence (β = 1.177); while environmental domain related factors included WHO clinical stage (β = -0.538), educational status(β = 0.549) and ART adherence(β = 1.078).Those who are young, with higher level of education, higher CD4 count and good access and adherence of ART, are likely to have better QOL among PLWHA in Zhejiang province. This suggests that in addition to ART, many other factors should be taken into consideration to improve the QOL of PLWHA. The relatively lower scores the subjects received in social relation and environmental domains also suggest that social relation and environmental interventions need to be strengthened.