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Gastric cancer with protein-losing gastroenteropathy is relatively rare worldwide. The most important problem for the treatment of these patients is their low nutritional status and protein level, which can cause severe postoperative complications. We report a 49-year-old Japanese female with a large gastric tumor and protein-losing gastroenteropathy successfully treated with neoadjuvant TS-1 combined with CDDP therapy. She had a type 5 tumor with partially cauliflower-like appearance. Her blood chemistry revealed low serum total protein (3.3 g/dl) and low albumin (1.7 g/dl). She was additionally diagnosed with protein-losing gastroenteropathy based on 99mTc-human serum albumin scintigraphy. Initial neoadjuvant chemotherapy decreased the size of the tumor and led to a marked improvement in her serum protein levels. She then underwent a total gastrectomy and lymph node dissection (D2) with a combined resection of the spleen and gallbladder. Therefore, neoadjuvant chemotherapy may provide a safe treatment before definitive surgery for gastric cancer with protein-losing gastroenteropathy.