Background: Gastric cancer is an important health problem across the world. Chemotherapy in combination with local treatment is standard treatment for locally advanced gastroesophageal cancers. The purpose of this investigation was evaluation of response and tolerability to neoadjuvant EOX regimen in locoregionally advanced gastric cancer. Materials and Methods: patients with locoregionally advanced gastric or EG junction adenocarcinoma enrolled in this study. Staging workup including chest and abdominal computed tomography (CT) scan, upper GI endoscopy, endoscopic ultrasonography (EUS), CEA, CBC, liver and renal function test were done. After treatment with 3 cycles of EOX regimen, endoscopic ultrasonography (EUS) and chest and abdominal CT scan was done to evaluate the response to neoadjuant chemotherapy. Results: The age of patients ranged from 37 to 78 years, with a mean age of 56.6 (SD=11.8). before chemotherapy, most patients were classified as stage III (98.8%) and after chemotherapy, most patients were classified as stage II (57.14%). only 28.5% of tumors were resectable before chemotherapy, but after chemotherapy 82.1% of tumors were resectable. 75% of tumors were downstaged after chemotherapy. Conclusion: With regard to acceptable response and downstaging of tumors and less toxicity with EOX regimen in locoregionally advanced gastric cancer, it seems that evaluation of this regimen as neoadjuvant chemotherapy in more advanced phase III clinical trial is necessary and logical.