Self-efficacy is associated with health behavior and medication adherence in persons living with HIV infection (PLWH). This paper describes self-efficacy, medication adherence, and quality of life (QOL), and it examines the relationships among these variables in PLWH in China. A cross-sectional survey of 199 patients was completed using the HIV Self-Efficacy Questionnaire and the QOL for Chinese HIV-Infected Questionnaire. Medication adherence was measured through direct questioning of pill-taking behavior. Results showed that self-efficacy for disease management was moderate, with a mean score of 6.61. Of the 199 patients, 157 (78.9%) reported that medication adherence was higher than 90%. The scores for dimensions of QOL ranged from 33.1 to 81.4, with six dimensions lower than 60. Stepwise regression analyses showed that self-efficacy, medication adherence, and drug use were significant predictors of QOL. These results suggest a need for intervention programs to improve self-efficacy and quality of life in Chinese PLWH.