Aim Quality of life is an essential outcome parameter in geriatric research and presents an important indicator for the evaluation of care treatments. The present study analyses potential impact factors on health-related quality of life (HRQOL) of nursing home residents (NHR) who are in pain. Methods Data came from the cRCT 'PIASMA'. Statistical analyses of 146 respondents were carried out by multiple linear regressions based on the EQ-5D index (Euroquol Quality of Life) as dependent variable. Potential impact factors were applied and categorised in five blocks: pain intensity and interference (according to the Brief Pain Inventory), intervention effect, sex and age, pain-related diagnoses, and scales regarding depressive symptoms and cognitive impairment (based on the Geriatric Depression Scale and the Mini-Mental State Examination). Results On average, residents showed a pain intensity of 18.49, a pain interference of 29.61, a MMSE score of 22.84, a GDS score of 5.65 and an EQ-5D index of 0.52. Residents with more diagnoses, more depressive symptoms, and a higher pain interference showed a significantly reduced HRQOL. Conclusion Findings underline the importance of identifying and applying treatment options for both pain (especially interference) and depressive disorders to maintain HRQOL of NHR.