BACKGROUND: Endoscopic submucosal dissection (ESD) has become a widely accepted, minimally invasive treatment for gastrointestinal submucosal tumors. It has been reported that humanistic nursing care with graded psychological interventions can effectively enhance patients' physical activity in patients, reduce postoperative complications, and improve their postoperative quality of life. AIM: To investigate the effects of combining humanistic care with graded psychological support on nursing satisfaction and quality of life in patients undergoing ESD for gastrointestinal submucosal tumors. METHODS: A retrospective analysis was conducted on the clinical data of 180 patients who underwent ESD surgery for gastrointestinal submucosal tumors at our hospital between March 2021 and February 2023. Patients were allocated into groups based on the nursing care they received: The control group, which received routine care ( RESULTS: Patients in the observation group experienced significantly shorter times to first postoperative meal, surgery, and hospital stay compared to the control group. After the intervention, the SAS score of the observation group was 43.17 ± 5.68, and the SDS score was 41.57 ± 6.52, both significantly lower than those of the control group, with SAS score of 52.38 ± 5.21 and SDS score of 51.23 ± 8.25. In addition, the observation group scored significantly higher in daily living, physical function, psychological well-being, and social functioning (80.01 ± 6.39, 83.59 ± 6.89, 81.69 ± 5.34, and 85.23 ± 6.05, respectively). Moreover, the observation group also exhibited higher satisfaction and self-efficacy scores and a lower incidence of adverse reactions compared to the control group ( CONCLUSION: For patients undergoing ESD for gastrointestinal submucosal tumors, humanistic nursing care in combination with graded psychological nursing care significantly shorten the times to first postoperative meal, surgery, and hospital stay, effectively alleviates anxiety and depression, improves quality of life and nursing satisfaction, and mitigate the incidence of adverse reactions.