Objective: To analyze the application effect of hierarchical group responsibility system of holistic nursing in Department of Gastroenterology. Methods: 655 patients in our hospital from August 2020 to January 2021 were selected as the research objects. They were randomly divided into experimental group (328 cases) and control group (327 cases) to explore nursing satisfaction, nursing quality score and clinical symptoms before and after nursing. Results: In the experimental group, 266 cases (81.10%) were very satisfied, 33 cases (10.06%) were satisfied and 29 cases (8.84%) were dissatisfied. The total number of satisfied cases (very satisfied + satisfied) was 299 cases (91.16%);In the control group, 167 cases (51.07%) were very satisfied, 63 cases (19.27%) were satisfied, 97 cases (29.66%) were dissatisfied, and 230 cases (70.34%) were satisfied. The nursing satisfaction of the experimental group was significantly higher than that of the control group; The nursing quality score of the experimental group was (91.67 ± 0.66), and that of the control group was (71.66 ± 0.88), which was significantly higher than that of the control group;The clinical symptom score of the experimental group was (2.42 ± 0.32), and that of the control group was (4.66 ± 1.11), which was significantly better than that of the control group.Conclusion: The application of hierarchical group responsibility holistic nursing mode in gastroenterology department can not only improve the nursing satisfaction of patients, but also improve the quality of nursing, promote the good development of patients' condition, and provide a comfortable treatment environment for patients, which is worthy of clinical promotion.