Abstract: Objective To explore efficacy of different surgical methods for gastric gastrointestinal stromal tumors(GISTs)at unfavorable positions and their impact on immune function. Methods A total of 92 patients with GISTs at unfavorable positions were selected and divided into laparoscopic group and laparotomy group, with 46 cases in each group. The laparotomy group underwent open GISTs resection, and the laparoscopic group underwent laparoscopic GISTs resection. Surgical indicators, inflammatory response and immune function indicators, postoperative complications, postoperative recurrence rate and survival rate at 1 year after operation were observed in the two groups. Results The intraoperative blood loss in the laparoscopic group was significantly less than that in the laparotomy group, and the postoperative first exhaust time and hospital stay in the laparoscopic group were significantly shorter than those in the laparotomy group(P<0.05). After surgery, the levels of immunoglobulin A(IgA)and immunoglobulin G(IgG)in the laparoscopic group were significantly higher than those in the laparotomy group, and the levels of C-reactive protein(CRP)and interleukin-6(IL-6)were significantly lower than those in the laparotomy group(P<0.05). The incidence of postoperative complications in the laparoscopic group was 8.68%, which was significantly lower than 23.91% in the laparotomy group(P<0.05). Conclusion Laparoscopic resection of GISTs has a definite therapeutic effect for patients with GISTs at unfavorable positions of the stomach. It can reduce intraoperative blood loss, completely remove the diseased tissue, shorten the length of hospital - stay and reduce postoperative complication. Besides, the surgery is conducive to postoperative recovery of gastrointestinal function.