ObjectiveThe objective of this study was to assess the prevalence of work-related stress (WRS) and its determinants among Huajian shoe manufacturing company employees in Dukem town, central Ethiopia. An institutional-based cross-sectional study was conducted from February to March 2016. Data were collected using pretested structured interviewer-administered questionnaires.ResultsThe mean age of the participants, 56.2% of whom were male was 25 (SD ± 5) years. The overall prevalence of work-related stress was 40.4% (95% CI 35.7, 45.3). Poor organizational support (adjusted odds ratio (AOR) 2.40, 95% CI 1.39, 4.77), inadequate work experience (AOR 3.77, 95% CI 1.68, 8.45), poor salary (AOR 7.04, 95% CI 3.39, 14.59), long working hours (AOR 3.40, 95% CI 2.00, 5.79), overtime work (AOR 2.24, 95% CI 1.10, 4.61), and poor physical environment (AOR 2.44, 95% CI 1.42, 4.19) were factors significantly associated with the stress. The prevalence of the stress was higher than what can be expected of many such employees. Poor organizational support, inadequate work experience, poor salary offers, long working hours, overtime work, and poor physical environment were significantly and independently associated with WRS. Establishing a functional collective agreement between employer and an employee trade union are needed to improve the problem.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3727-5) contains supplementary material, which is available to authorized users.