Aim: To investigate the incidence of pancreatic cancer-related depression and the relationship between symptoms of depression and the quality of life (QoL) of patients. Methods: 262 inpatients with cancer of the digestive system (pancreatic cancer, liver cancer, esophageal cancer, gastric cancer, and colorectal cancer) from four Guangzhou hospitals were enrolled into the study between June 2007 and June 2009. The Hamilton Rating Scale for Depression-24 questionnaire was used to assess the degree of depression. QoL of all patients was evaluated by EORTC QLQ-C30. Additionally, EORTC QLQ-PAN-26 was used for patients with pancreatic cancer. Results: The incidence of depression among pancreatic cancer patients was significantly higher than among other digestive cancers. More pancreatic cancer patients suffered severe depression than those with liver cancer and gastric cancer. Compared with other groups with depression, QoL of pancreatic cancer patients in each functioning scale was significantly worse, while the symptoms of fatigue and pain were significantly severe. QoL of pancreatic cancer patients with depression in role, emotional, and social functioning were sharply poorer than those without depression. The symptoms of fatigue, pain and appetite loss in cancer patients with depression were significantly more frequent than those without depression. Conclusion: Compared with other cancers of the digestive system, depressive symptoms are common psychological disturbances in pancreatic cancer patients. Moreover, depression significantly lowers QoL in pancreatic cancer patients.