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Purpose: This study aimed to determine the moderating effect of self-esteem on the perception of death and the meaning of life among hospital nurses. Methods: The participants were 167 nurses working in two tertiary general hospitals located in city B. Data were collected from September 8 to 21, 2022. SPSS/WIN 29.0 was used for analysis along with t-test, ANOVA, Pearson correlation coefficients, and hierarchical multiple regression. Results: The study showed that the meaning of life was significantly correlated with the perception of death (r=.34, p<.001) and self-esteem (r=.31, p<.001). Self-esteem significantly moderated the relationship between the perception of death and the meaning of life (F=16.00, p<.001). Conclusion: Self-esteem may moderate the relationship between the two factors. This means that nurses with higher self-esteem have a greater tendency for their perception of death to positively impact their meaning of life. Therefore, for hospital nurses to discover the meaning of life, it is necessary to develop and apply a self-esteem enhancement program specialized for each clinical career.