Patients' cognitions about their disease and treatment are important mediators between health and quality of life of patients with chronic diseases and also explain the occurrence of individual differences in individuals' adjustment to chronic disease. The aim of this study was to examine the relationship between illness cognitions and health-related quality of life among adult patients with inflammatory bowel disease. Self-report data on illness cognition and health-related quality of life were collected from 118 people with Crohn disease or ulcerative colitis. Illness cognition of greater helplessness significantly predicted health-related quality of life in patients with inflammatory bowel disease. A relative contribution of acceptance and perceived benefits was not confirmed as a predictor of health-related quality of life. The other variables (type of disease, duration of disease, age, and episode of relapses) did not have statistical significance, except for gender. Results demonstrate that experiencing helplessness in relation to the disease, its treatment, and consequences can be generalized to patients in all areas of daily life, leading to deterioration in their overall psychological and physical functioning. These results can provide useful indicators of potential patient's adherence in treatment and self-management of inflammatory bowel disease.