Abstract: Objective: To explore the impact of quality of life on psychological distress in patients with HIV, as well as the mediating role of self-efficacy and the moderating role of social support.Methods: The World Health Organization (WHO) quality of life questionnaire for HIV brief version (WHOQOL-HIV BREF), Psychache Scale (PAS), General Self-Efficacy Scale (GSES), and Social Support Revalued Scale (SSRS) were used to survey 172 Aids patients, respectively.Results: The quality of life of HIV patients had a great negative predictive effect on their psychological distress (β=-0.356,SE=0.071,P＜ 0.001), self-efficacy played a partial mediating role between quality of life and psychological distress (β=-0.145,SE=0.041,95%CI:-0.231~-0.071), and the mediating effect accounted for 28.94% of the total effect.And high level of social support had a moderating effect on quality of life and self-efficacy.Conclusion: A moderated mediating model exists between quality of life and psychological distress in patients with HIV, whereby quality of life can exert its effect on psychological distress through its self-efficacy, and the effect of quality of life on self-efficacy is modulated by the level of social support.