Conversion therapy for gastric cancer (GC) has been the subject of much recent attention. GC patients with bulky lymph node metastases were usually considered oncologically unresectable and surgery could be challenging and tumor shrinkage may serve to facilitate resection. Previous studies reported satisfactory survival data were obtained in the series of neoadjuvant studies with bulky N disease. However, the evidence of combining neoadjuvant chemotherapy with targeted therapy for patients with bulky N disease is inadequate. We report a 52-year-old man who was diagnosed with unresectable GC with bulky lymph node metastases after endoscopic biopsy and abdominal enhanced computed tomography (CT) examination. Histopathology confirmed poorly differentiated adenocarcinoma at the junction of the antrum and the body of the stomach. Abdominal enhanced CT showed marked thickening of more than two-thirds of the stomach wall and multiple enlarged and coalesced perigastric and extragastric lymph nodes. The clinical staging was cT4aN3M0. The patient was administered two cycles of S-1 and oxaliplatin (SOX regimen) plus apatinib. Repeat abdominal enhanced CT demonstrated decrease in stomach wall thickness and in the sizes of all perigastric and extragastric lymph nodes (<1.0 cm). D2 gastrectomy with para-aortic lymph node dissection was performed after 5 weeks. Pathological examination of resected specimen revealed a ypT4bN0M0 poorly differentiated adenocarcinoma. All 140 lymph nodes that were examined were negative. SOX chemotherapy regime was advised after surgery, but had to be discontinued after two cycles because of severe side effects. The patient has been followed up regularly for more than 2 years with enhanced abdominal CT and the examination of tumor markers. No recurrence or metastasis has been identified till the time of submission of this article. Our treatment experience might provide a reference for the treatment of GC patients with bulky lymph node metastases.