Aims To explore whether pain intensity has an indirect effect on quality of life through mediation of depression in patients with neuropathic pain (NeP). Design An observational, questionnaire-based, cross-sectional study. Methods A convenience sample of patients suffering from NeP were enrolled from June 2015 - May 2016. Three questionnaires were used to collect data of pain intensity, Quality of life and depression. Andrew Hayes' PROCESS macro modelling tool for the SPSS software, based on the mediation Bootstrap confidence interval method, was used to analyse the mediation effect. Results Both pain intensity and depression correlated negatively with the quality of life of patients. The indirect effect of pain intensity on the quality of life through depression was negative. Conclusions Increased pain intensity and depression were associated with a decreased quality of life in patients suffering from NeP and pain intensity had an indirect effect on the quality of life of patients through depression. Impact A low quality of life and depression are commonly seen in patients with NeP. However, little is known about the relationship between pain, quality of life and depression. Both pain intensity and depression had some negative effect on quality of life in patients with NeP. Pain intensity had an indirect effect on quality of life through a mediation effect of depression in patients with NeP. When caring for patients with NeP, nurses should assess depression routinely and try to alleviate it.