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Objectives: The aim of this study was to examine the effects of physiological indicators, uncertainty, and grit on the self-management of hemodialysis patients and to identify ways to improve the quality of life of hemodialysis patients. Methods: A convenience sample of 140 patients receiving hemodialysis was selected. Data were collected using a structured questionnaire and also obtained from medical records. The collected data were analyzed using descriptive statistics, t-test, ANOVA, Pearson correlations, and multiple regression analysis using the SPSS/WIN 25.0 program. Results: The self-management of participants undergoing hemodialysis showed a significant relationship with hemoglobin, total protein, Ca*P, uncertainty, and perseverance of effort. The significant factors influencing self-management were Ca*P (β =-.18, p=.014), perseverance of effort (β=.40, p<.001), and monthly income (β=.18, p=.006). These variables explained 31.4% of the variance in self-management. Conclusions: The perseverance of effort in hemodialysis patients was confirmed to be the main variable influencing self-management. Therefore, to improve the self-management of hemodialysis patients, it is necessary to develop interventions and programs to improve PE.