Background: An overall survival (OS) benefit with PCT over surgery alone for locally advanced gastric cancer was seen in phase III trials. The best PCT regimen is uncertain and options based in infusional 5-FU or capecitabine have cost limitation in the context of Brazilian public health system. The combination of cisplatin and irinotecan is active in the metastatic setting, with no need of ambulatory infusion devices. The aim of this study is to evaluate safety and preliminary efficacy of this scheme as PCT. Methods: This prospective single arm study included patients (pt) with locally advanced gastric cancer, T3/T4 and/or evident lymph node involvement, to receive PCT cisplatin (30 mg/m2) and irinotecan (60 mg/m2) D1 and D8, each 21 days, in total of 6 cycles (Cy). Results: Between June/2011 and January/2014, 25 pt were included, with the following characteristics: 64 years (34-78) as median age; 10 (40%) pt with intestinal subtype and 10 with diffuse; 24% of cases were proximal gastric tumors; 20% had dysphagia and 24% bleeding signs before treatment. The median number of Cy before surgery was 3; 19 (76%) pt had surgery and 8 (32%) re-started Cy after surgery. Toxicity grade 3 or 4 was seen in 13 (52%) pt and 3 had unexpected arterial ischemic events. Radiologic progression occurred in 8 (32%) pt. Of the 21 tissue samples available, the expression of MLH-1, HER-2 (+++), p53, p16, Ki67 and EGFR was detected in 100% (21/21), 9.5% (2/21), 90.5% (19/21), 81% (17/21), 100% (11/21 < 50% and 10/21 > 50%) and 100% (10/21 +1/2 and 11/21 +3/4) of the cases, respectively. No correlation was seen between them and pathologic response. With a median follow up of 382 days, 13 (52%) pt were alive and the median OS was 15.2 (IC95% 4.9-24.5) months. In a univariate analysis, dysphagia, less than 3 Cy, progressive disease and neutrophil-to-Lymphocyte ratio (NLR) > 2, were significantly related to shorter OS. In multivariate analysis, only NLR > 2 (p = 0.019) and dysphagia were negatively impacting on OS (p = 0.02). Conclusions: Although PCT with cisplatin and irinotecan for evident locally advanced gastric cancer showed acceptable resection rate and local control, the overall prognosis was limited in this setting.