Introduction: Chronic kidney disease is a serious problem and patients need active self-care. This study focuses on the relationship between self-care and its predictive factors in hemodialysis (HD) patients. Methods: This multicenter correlational study was conducted on 201 HD patients referring to HD centers in the west of Tehran, Iran. A multi-stage sampling method was used to select the samples. Data were collected using self-care Scale, Paloutzian-Ellison Spiritual Well-Being Scale, and Connor Davidson Resilience Questionnaires. Data were analyzed using SPSS software version 13 and descriptive statistics and linear regression with stepwise method. Results: The mean (SD) scores of self-care, resilience, and spiritual well-being were 35.5 (5.69), 53.4 (12.94), and 97.4 (17.9), respectively. Univariate analysis showed that self-care had a statistically significant relationship with gender, occupation, education, being diabetic, and hyperlipidemia. Self-care positively correlated with the resilience and negatively correlated with age. Multivariate regression indicated that the resilience (β=0.78, P=0.001), being diabetic (β=-0.09, P=0.01), and age (β=-0.11, P=0.005) could be predictors of self-care. These variables accounted for 78% of variance in self-care in HD patients. Conclusion: Our results showed that resilience was positively correlated with self–care, but being diabetic and age were negatively correlated with self-care in HD patients. Therefore, the health care providers should pay more attention to HD patients who are diabetic and older, as they are at a higher risk of having impaired self-care.