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Purpose: Health-related quality of life (HRQOL) is an increasingly critical outcome of chronic illness care. However, its disease-independent attributes, particularly its spiritual resilient indicators, for people with Parkinson's disease (PD) have not been explicitly examined. This study aimed to (i) assess the associations between psychological distress, spiritual resilience and HRQOL, and (ii) examine the mediating effects of spiritual resilience on psychological distress and HRQOL amongst individuals with PD. Methods: This is a secondary data analysis of the baseline data of a clinical trial that involved 138 individuals with PD. The subjects completed a structured questionnaire assessing psychological distress in terms of anxiety and depression, spiritual resilience in terms of perceived affliction and perceived equanimity, severity of motor symptoms and disease-specific HRQOL. Results: Analysis by independent t test suggested that distressed individuals with PD demonstrated less spiritual resilience and presented poorer HRQOL than non-distressed individuals with PD. Multiple linear regression models revealed that high emotional distress was associated with low spiritual resilience and poor HRQOL. The mediation analysis found that after simultaneously controlling for the degree of perceived affliction and perceived equanimity, a significant reduction was observed in the direct effect between psychological distress and HRQOL. This result indicated the partially mediating roles of perceived affliction and equanimity in the pathways between psychological distress and HRQOL. Conclusion: In order to enhance HRQOL, PD interventions should address the spiritual resilience of patients in addition to providing psychological care and physical relief of symptoms. [ABSTRACT FROM AUTHOR]