Abstract: Objective To investigate the relationship of single nucleotide polymorphisms（SNPs）of phosphatase and tensin homolog deleted on chromosome ten（PTEN）and phosphatidylinositol 3-kinase catalytic alpha polypeptide（PIK3CA）of PI3K/Akt pathway with efficacy of platinum-based chemotherapy in patients with advanced gastric cancer. Methods Four tag SNPs of PTEN genes（rs532678，rs926091，rs11202609 and rs17431184）and 3 tag SNPs of PIK3CA genes（rs2459693，rs3729679 and rs12494623）from Beijing Han population database published by International HapMap Project（Hap Map）were screened using Haploview software.The peripheral blood samples of 158 patients from Jan 2012 to Dec 2015 with advanced gastric cancer were collected and MassArray mass spectrometry array was used to determine genotype. The short-term efficacy of platinum-based chemotherapy was evaluated by RECIST 1.1 creteria after two cycles of chemotherapy. Then the patients were assigned into sensitive group （CR+PR） and insensitive group（SD+PD）. The relationship between sensitivity and above SNPs genotype／allele was analyzed. Results In 158 patients with advanced gastric cancer，the genotypes and the allele distribution of 7 SNPs in PTEN and PIK3CA genes were in line with the Hardy-Weinberg equilibrium. There were 83 patients in sensitive group（3 cases of CR and 80 cases of PR）and 75 patients in insensitive group（42 cases of SD and 33 cases of PD）after 2 cycles' chemotherapy. PIK3CA rs3729679 and rs12494623 SNPs were associated with the sensitivity of platinum-based chemotherapy in patients with advanced gastric cancer. Patients harboring mutation genes（rs3729679 G, rs12494623 T） had rather low sensitivity and an increased risk of insensitivity with the statistical significant differences（P＜0.05）. The remaining PIK3CA SNPs and PTEN SNPs loci were unrelated with sensitive rates and risk of insensitity（P＞0.05）. Conclusion PIK3CA rs3729679 and rs12494623 SNPs were associated with the sensitivity of platinumbased chemotherapy in patients with advanced gastric cancer. Patients harboring rs3729679 G or rs12494623 T are not sensitive to chemotherapy and have a higher risk for being insensitive to chemotherapy. It is helpful to predict the efficacy of platinum-based chemotherapy in patients with advanced gastric cancer.