Abstract: Objective To evaluate the effect of surgical treatment for patients with locally advanced, imatinib-resistant gastrointestinal stromal tumors (GIST). Methods A retrospective analysis was performed in 34 patients with locally advanced, imatinib-resistant gastrointestinal stromal tumors treated in our hospital from January 2009 to September 2017. Of the 34 cases, 24 patients underwent surgery combined with imatinib treatment served as combinative treatment group, and 10 patients received imatinib alone as imatinib group. The treatment benefit of the two groups was compared, including progression-free survival (PFS) and overall survival (OS). Results There was no significant difference in gender, age and primary site of the tumor between the two groups(all P＞ 0.05). The PFS and OS of the combinative treatment group were longer than those ofimatinib group (PFS, 17.8 months vs 10.5 months, P=0.019; OS, 48.9 months vs 30.7 months, P=0.011). Conclusion The clinical effect of surgery combined with imatinib is superior to drug therapy alone on patients with locally advanced, imatinib-resistant gastrointestinal stromal tumors.