Purpose: This was a correlation study to identify the relationship of spiritual well-being, hope on fatigue in cancer patients on chemotherapy. Methods: The subjects completed structured questionnaires: the ‘Spiritual Well-being Scale', developed by Paloutzian & Ellison, 'Hope Scale', developed by Kim & Lee and 'Fatigue Scale', developed by Mendoza et al. Data were collected from 120 patientsat two general hospitals and were analyzed using t-test, ANOVA & Sheffe's test, Pearson’s correlation coefficients and multiple stepwise regression. Results: Participants with higher fatigue had lower scores for hope (r=-.36, p<.001) and lower scores for spiritual well-being (r=-.23, p = .011). Participants with higher scores for hope had higher scores for spiritual well-being (r=.61, p<.001). The factors seen as contributing to fatigue were hope, financial burden of treatment, period of religious life, living with spouse, and reported pain. These variables explained 32.3% of the variance in fatigue. Hope with 13% was the most influential. Conclusion: The fatigue of the cancer patients on chemotherapy can be reduced if hope is improved, and hope can be improved if the spiritual well-being is improved. Therefore, we suggest developing a nursing intervention program that leads to improve hope and spiritual well-being of the cancer patients on chemotherapy for reducing fatigue.