ObjectiveThe impact of pain and depression on health-related quality of life (QoL) is widely investigated, yet the pain-depression interactions on QoL remain unclear. This study aims to examine the pain-depression-QoL mediation link.MethodsPain severity were assessed in a sample of Chinese professional teachers (n = 385). The subjects were also assessed on depressive symptoms and QoL. Regression models were fitted to evaluate the pain-depression-QoL relationships.ResultsAbout 44% of the sample had 3-5 painful areas in the past 3 months. Shoulder pain (60%) and headache (53%) were common painful areas. The results of regression analyses showed that pain mediated the effects of depression on the mental aspect of QoL (standardized β = -0.111; Sobel test: z = -3.124, p < 0.005) whereas depression mediated the effects of pain on the physical aspect of QoL (standardized β = -0.026; Sobel test: z = -4.045, p < 0.001).ConclusionsOur study offered tentative evidence that pain and depression impacted differently on the mental and physical aspect of QoL. As these findings were based on a Chinese teacher sample, future studies should employ more representative samples across cultures to verify the present data.