The aim of this study is to explore how organizational support and quantitative workload influence work‐related fatigue. We collected 688 questionnaires from product line workers in 6 Chinese iron and steel factories. Confirmatory factor analysis and bootstrapping were used in the data analysis, and structural equation modeling was adopted to test the hypothetical model. The results showed that intrinsic motivation fully mediates the relationship between organizational support and work‐related fatigue, while partly mediating the relationship between quantitative workload and work‐related fatigue. The results of this study indicate the potential benefit of improving motivation to alleviate work‐related fatigue. Finally, this study puts forward suggestions for future studies.