Objectives: Patients with peritoneal metastasis have significantly poor prognosis. We have performed the conversion surgery when peritoneal metastasis disappears by chemotherapy for those patients (J Gastrointest Surg. 2019;23:1758-1766). A regimen of S-1 combined with oxaliplatin (SOX) has been used widely as the first line regimen for advanced gastric cancer. To further improve the antitumor efficacy for gastric patients with peritonitis carcinoma, we devised the triplet regimen of a nab-paclitaxel (nanoparticle albumin-bound paclitaxel), S-1 and oxaliplatin, named the 'NSOX regimen' as a new and powerful treatment. Nab-paclitaxel has effective transferability to tumor tissues and strong antitumor effects for peritoneal metastasis. A phase I study of this regimen was performed to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in gastric cancer patients with peritoneal metastasis. Methods:The NSOX regimen involved 21-day cycles with escalated doses of nab-paclitaxel (50 (level 1)-80 (level 4) mg/m² on days 1 and 8) and fixed doses of oxaliplatin (100 mg/ m² on day 1) and S-1 (80 mg/m²/day on days 1 to 14). Results: Six gastric cancer patients with peritoneal metastasis were enrolled. At dose level 1, dose-limiting toxicities (DLTs) were not observed in all patients. The MTD was determined to be dose level 2, as 2 of 3 patients experienced DLTs, grade 4 non-hematological toxicities. One patient experienced acute myocardial infarction, and the other patient developed jejunal perforation. There were no treatment-related deaths. Therefore, the RD was determined to be dose level 1. Conclusions: The NSOX regimen was shown to be a tolerable regimen and may be a promising triplet therapy for gastric cancer patients with peritoneal metastasis. We will evaluate the long-term safety and efficacy of the NSOX regimen in a phase II study. (Registration number: UMIN000030909)