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Purpose: This study aimed to investigate variables affecting health-related quality of life of manufacturing industry workers. Methods: We used data from 200 survey questionnaires collected from a vehicle manufacture factory located in Ulsan metropolitan area. The participants were manufacturing workers. The data were analyzed using t-test, one-way analysis of variance, and Scheffé’s test to identify differences among variables. Pearson’s correlation coefficient and stepwise multiple regression were used to identify variables that affected health-related quality of life. Results: The findings revealed that occupational stress and quality of sleep were statistically significant variables of the physical component score with an explanatory power of 42.2%. Occupational stress, depression, and religion were statistically significant variables of the mental component score with an explanatory power of 43.3%. Conclusion: Continuous monitoring and appropriate intervention for occupational stress, quality of sleep, and depression are needed to improve manufacturing workers’ health-related quality of life.