This study investigated health-related quality of life and identified factors affecting it among people with the HIV in South Korea. A total of 243 people living with HIV participated in this cross-sectional survey. Data were collected from five hospitals between November 2021 and August 2022 using structured online questionnaires. Data were analyzed using descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Spearman's rho analysis, and Tobit regression analysis because a significant ceiling effect was observed for the dependent variable. The mean score for the health-related quality of life was 75.74 ± 16.48. The significant factors that positively influence the health-related quality of life were "employment" (B = 4.57, p = .035), "not participating in the self-help group" (B = 6.10, p = .004), "higher self-efficacy for managing symptoms" (B = 1.32, p = .036), "higher self-efficacy for getting support/help" (B = 0.95, p = .035), and "higher self-efficacy for managing fatigue" (B = 2.80, p < .001) in the Tobit regression analysis. The results suggest that interventions to increase self-efficacy should involve developing programs and policies for people living with HIV. There is a need for efforts to provide healthcare services linked to employment support, as well as to establish a social environment in which they can work without stigma. Further, self-help groups could be utilized as intervention channels.