This study evaluated the correlations between spiritual beliefs and health-related quality of life (HRQOL) of hemodialysis (HD) patients in Taiwan. Participants had to complete two questionnaires: the 36-item Short Form Health Survey Questionnaire and the Royal Free Interview for Spiritual and Religious Beliefs. They were then divided into three groups according to their strength of spiritual beliefs-having no, weak, or strong beliefs. Demographic, clinical, and laboratory data among groups were compared. Correlations between spiritual beliefs and HRQOL were then determined by the analysis of covariance and the post hoc Scheffe tests. Six hundred thirty-three patients completed the study. There were more women in the group of patients with strong beliefs (P = 0.005) and more less-educated patients in the group of patients with weak beliefs (P = 0.005). Patients with no or with strong spiritual beliefs had higher role physical (P = 0.01) and social functioning (SF) (P = 0.001) scores than patients with weak beliefs. After adjustment for gender, age, marital status, education, comorbidities, and time on dialysis, patients with no or with strong spiritual beliefs were found to have higher SF scores (P = 0.02) than patients with weak beliefs. HD patients with no or strong spiritual beliefs had higher SF HRQOL than those with weak spiritual beliefs.