ObjectiveTo evaluate the influence of pathological differentiation in the effect of preoperative chemo-therapy for patients with locally advanced gastric cancer (LAGC). MethodsThirty-two patients with LAGA received preoperative chemotherapy with oxaliplatin and capecitabine (XELOX regimen).According to the pathological examina-tion, patients were classified into better (well and moderate, 16 cases) and poorly (16 cases) differentiated groups, and the clinical response rate, type of gastrectomy, and negative tumor residual rate were compared between the two groups.Morphological changes and toxic reactions were monitored after chemotherapy. ResultsThe results showed that the clinical response rate in the better differentiated group was significantly higher than that in the poorly differentiated group (100% vs.6.4%, P=0.000).The partial gastrectomy rate in the better differentiated group was significantly higher than that in the poorly differentiated group (87.5% vs.25.0%, P=0.000).A significant shrinking of tumor size and necrosis of tumor tissues caused by chemotherapy could be observed. ConclusionThe better differentiated group with locally advanced gastric cancer is suitable for preoperative chemotherapy with XELOX regimen, and as a result of effective preoperative chemotherapy, much more gastric tissue can be preserved for better differentiated group.