Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 53 4 2024 04 08 809 817 Min-Jeong Park School of Nursing, Kunsan National University, Gunsan, Republic of Korea Hwee Wee School of Nursing, Kunsan National University, Gunsan, Republic of Korea 2022 10 10 2024 04 08 Background: Middle-aged women have lower health-related quality of life (HRQoL) than men, and women's participation in economic activities is an important issue. In this study, the middle-aged female population was classified by economic activity participation to explore HRQoL and to identify related factors. Methods: We obtained data from the 2017 Korea Health Panel Survey (N = 1857 women aged 50–64 years), analyzed with chi-squared tests, t-tests, analyses of variance, and multiple regression analyses. HRQoL was measured with the Euro QoL-5 Dimensions index, and four demographic factors, four health behavior factors, and ten health status factors were entered. Results: HRQoL was lower in the economically inactive group compared to the active group. Education, physical activity, chronic disease, vision problem, dental problem, activity restriction, frustration, and anxiety were associated with HRQoL in both groups. Spouse and household income were additional predictors identified only in the economically inactive group, and the 10 factors explained 36.0% of the variance. In the economically active group, drinking, sleeping time, hearing problem, stress, and depression were additional predictors identified, and the 13 factors explained 23.0% of the variance. Conclusion: Healthcare providers should consider both common predictors between economically active and inactive middle-aged women as well as predictors that were unique to each group to improve their HRQoL. https://ijph.tums.ac.ir/index.php/ijph/article/view/30048 https://ijph.tums.ac.ir/index.php/ijph/article/download/30048/8209