Objective: This study aimed to determine the determinants of depressive symptoms (DSS), sleep disorders, anxiety, and health-related quality of life (HRQOL) in maintenance hemodialysis patients. Methods: A descriptive, correlational design was used to evaluate 1330 maintenance hemodialysis patients. Participants were interviewed face-to-face to collect demographic information and disease characteristics, assess self-control schedules, and survey health status. Correlation analysis, t test, analysis of variance and regression analysis were used for analysis. Results: According to the recommended classification of DSS, 56.4% of the patients had mild (31.1%), moderate (18.9%) or severe (6.2%) depressive symptoms. The pain caused by illness was positively correlated with depression, and negatively correlated with resourcefulness (- 0.28), PQOL (-0.24) and MQOL (- 0.42). Education was negatively correlated with depression (-0.19), positively correlated with resourceiness (0.28), PQOL (0.16) and MQOL (0.28). Age was positively correlated with depression and resourceiness, and negatively correlated with PQOL (- 0.48) and MQOL (- 0.18). Highly educated participants were more likely to have better PQOL and MQOL. Lower DSS. Higher monthly household income is more likely to have better MQOL and lower DSS, and there is no correlation with PQOL. Higher education is associated with more sleep disturbances, resourcefulness, and anxiety; The higher the monthly income, the lower the anxiety and the higher the resourcefulness; Stage II patients have more sleep disorders, resourcefulness, anxiety; People with depression tend to have more sleep disturbances, resourcefulness, and anxiety. Conclusion: Nursing professionals need to spot mental illness and must be especially vigilant for those with mental retardation and sleep disorders. The impact of resourcefulness on health-related mental and physical quality of life was identified in maintenance hemodialysis patients, where resourcefulness played a beneficial role as a mediator of symptoms from pain to depression, PQOL, and MQOL, respectively. Resourcefulness has an effect on reducing depressive symptoms in maintenance hemodialysis patients.