This study aimed to determine the effect of depression between the health-related quality of life and pain in elderly persons with physical disabilities. A total of 111 patients who were treated at hospital B (Seoul, Daejeon, Daegu, Gwangju, and Busan) participated in the Survey. The SF-36 Health Assessment was used to determine the quality of life of subjects, the Korean version of the Geriatric Depression Scale-Short form to assess the level of depression, and Numeric Rating Scale to determine the level of pain. To determine the moderating effect of depression on the relationship between quality of life and pain, simple regression analysis, and the Sobel test were performed. There was a significant negative correlation between health-related quality of life and pain (r<-.3, p<.05), and a significant positive correlation between depression and pain (r=.251, p<.05). Thus, health-related quality of life had a simple regression relationship with depression and pain. Depression also showed a mediating effect between health-related quality of life and pain. The results of this study suggest that depression mediates between pain and quality of life.