Background: Nurses displayed low levels of subjective well-being and high turnover intention. How to enhance the subjective well-being and decrease the turnover rate of nurses is of great importance. However, little is known about whether work engagement mediates between character strengths and subjective well-being. The study aims to explore character strengths, work engagement and subjective well-being in nurses, and to determine whether work engagement plays a mediating role between the relationship. Material and Methods: From December 2017 to December 2018, 450 Chinese registered nurses completed the character strengths scale, work engagement scale, and subjective well-being scale. The relationship between study variables was tested by Pearson correlation. The mediating effect of work engagement was tested by the bootstrap method. Results: The results indicated the following: (1) the 4 elements of character strengths and work engagement were significantly and positively correlated with subjective well-being; (2) character strengths could significantly predict both work engagement and subjective well-being; (3) work engagement played a mediating role in this relationship. Conclusions: Character strengths affect subjective well-being in Chinese registered nurses, and work engagement plays a mediating variable among the relations. Therefore, nurses are encouraged to foster their character strengths and improve their level of work engagement for their subjective well-being. Following the results, the study recommends that nursing managers be aware of the importance of using character strengths in nursing work, taking actions to excavate nurses’ character strengths and encouraging nurses to use character strengths in clinical work to promote engagement and well-being. In the meantime, interventions to improve the level of subjective well-being based on nurses’ character strengths should be considered. Med Pr. 2022;73(4):295–304