BACKGROUND: ICU nurses frequently confront lengthy working hours, elevated job intensity, heavy medical responsibilities, round-the-clock shifts, and a comparatively closed working environment. The high-risk, high-intensity, high-stress nature of the profession may prompt nurses to consider resignation, culminating in a significant shortage of nursing staff, adversely affecting the health and well-being of nurses. Necessitating a comprehensive investigation into the factors influencing their subjective well-being and the interrelations among these factors, thereby establishing a theoretical foundation for a more focused intervention program aimed at enhancing the subjective well-being of nurses. METHODS: This study employed a cross-sectional design in accordance with STROBE criteria. Two hundred forty-seven ICU nurses from four tertiary general hospitals were intentionally chosen to take an online survey. Metrics encompassed self-efficacy, work-family balance, and subjective well-being. RESULTS: The findings demonstrated that self-efficacy strongly influenced nurses' work-family balance and subjective well-being. The work-family balance served as a mediating factor in the association between self-efficacy and subjective well-being. Mediation analysis indicated a substantial overall influence of self-efficacy on subjective well-being (β = 0.758, p <
0.01). In addition, self-efficacy had a direct effect on subjective well-being (β = 0.575, p <
0. 01), on work-family balance (β = 0.458, p <
0. 01), and work-family balance had a direct effect on subjective well-being (β = 0.399, p <
0.01). CONCLUSION: This study found that among nurses in ICU have moderate levels of self-efficacy and subjective well-being, which are positively correlated. This suggests that improving the self-efficacy and work-family balance of ICU nurses may help enhance their subjective well-being levels.