The purpose of this study was to assess the pre- and postoperative quality of life (QOL) of patients with gastrointestinal cancer and to investigate the relationship between QOL and various psychological and clinical factors. Eighty-five patients who underwent surgery for gastrointestinal cancer and 26 control patients undergoing surgery for digestive diseases other than cancer were interviewed. Two tests were administered to assess QOL and psychological status respectively: the Japanese-language version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the Japanese-language version of the Hospital Anxiety and Depression Scale (HADS). Each test was administered before surgery, before discharge, and 6 months after discharge. Gastrointestinal tumors were localized to the stomach, colon, or rectum in 88% of cases and classified as advanced stage or early stage according to staging protocols. Changes in EORTC QLQ-C30 subscale scores over time were compared among advanced stage, early stage, and control patients. All groups showed significant changes in subscale scores of QOL; the scores of the advanced-stage group indicated worse QOL than the early-stage and control groups in a lot of areas. The physical function (PF2) QOL subscore was influenced by diagnosis, postoperative complications, medical equipment at discharge, and the length of admission and negatively correlated with depression and anxiety. These results suggest that QOL in gastrointestinal cancer patients is variable over time and is influenced by various clinical factors. Therefore, consideration of these clinical factors is paramount to the optimal care of gastrointestinal cancer patients.