Purpose: This study is to identify factors related to health-related quality of life in one-person households across the life cycle by analyzing data from the 2021 Korean National Health and Nutrition Examination Survey. Methods: The subjects of one-person households were divided into 195 young adults, 273 middle-aged people, and 490 elderly people according to life cycle. Data were analyzed by complex sample cross tabulation, complex sample t-test, complex sample ANOVA, and complex sample multiple regression analysis using IBM SPSS 26.0. Results: In young adults, subjective health status, daily activity limitation, and stress level explained 41% of health-related quality of life, and in middle age, income level, education level, occupation, marital status, subjective health status, stress level, and depression had a 60% explanatory power. In old age, education level, subjective health status, daily activity limitation, stress level, and depression explained 53% of health-related quality of life. Conclusion: In order to effectively improve the health-related quality of life of one-person households, it is necessary to establish a customized program considering the influencing factors across the life cycle and systematically manage it according to the flow of the life cycle.