Objective To investigate the relationship between symptoms of pancreatic cancerrelated depression and quality of life of patients. Methods Fifty inpatients with pancreatic cancer from 3 Guangzhou hospitals between June 2007 and October 2008 were enrolled. Hamilton rating scale for depression-24 (HAMD-24) questionnaire was used to assess the degree of depression. Quality of Life (QoL) was evaluated by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) and QLQ-PAN-26 respectively. Results Thirty-nine (78.0%) of these patients reported depression and 12 patients (30. 8%) had severe depression. The incidence of depression in pancreatic cancer patients with chemotherapy was 92.3% (24/26), which was significantly higher than that of patients with surgical therapy (62.5%, 15/24) (P = 0.011). The QoL of pancreatic cancer patients with depression in role functioning, emotional functioning and social functioning was significantly worse than that of patients without depression. The symptoms of fatigue, pain and appetite loss in pancreatic cancer patients with depression were significantly more than those without depression (P < 0.05). Conclusions Depressive symptoms are common psychological disturbance in pancreatic cancer patients. Moreover, depression significantly lowers quality of life for pancreatic cancer patients.