BackgroundClinical nurses are essential to healthcare, but they experience high rates of depression, anxiety, and sleep disturbances. This study examined the relationships among occupational stressors, sleep problems, mindfulness, and psychological well-being in hospital nurses.MethodsIn a cross-sectional study of 416 clinical nurses from a tertiary general hospital in China, we assessed mindfulness, depression, anxiety, sleep quality, insomnia, and work stress. Multivariate logistic and linear regression models explored independent factors associated with depression, focusing on mindfulness dimensions.ResultsDepression was highly prevalent (56.0%), as were clinical insomnia (52.4%) and poor sleep quality (54.6%). Multivariate analysis identified poor sleep quality (OR = 4.19, 95% CI: 2.47–7.12), insomnia (OR = 2.15, 95% CI: 1.22–3.75), and high work stress (OR = 2.12, 95% CI: 1.25–3.60) were significantly associated with an increased risk of depression. Notably, of the five mindfulness facets, only non-reactivity associated with a reduced risk of depression (OR = 0.88, 95% CI: 0.79–0.98). This association was consistent, showing a significant linear association in multivariate linear regression (B=-0.509, p<0.001).ConclusionThis study highlights the severe mental health burden among clinical nurses and demonstrates mindfulness non-reactivity is significantly associated with a lower risk of depression. These findings provide a preliminary empirical basis for future intervention studies targeting mindfulness facets.