OBJECTIVE: To explore the association between CYP3A4 gene polymorphism and the sensitivity of advanced gastric cancer patients to paclitaxel chemotherapy. METHODS: 67 patients diagnosed as advanced gastric cancer were selected from the Third Affiliated Hospital of Kunming Medical University during Mar.-Sep. 2014. Blood samples were collected before chemotherapy, and PCR-RFLP analysis was performed to detect CYP3A4 gene polymorphism. All patients were given two-drug chemotherapy based on paclitaxel. Therapeutic efficacy was evaluated by solid tumor therapeutic efficacy evaluation criteria, and objective remission rate (ORR) was used to evaluate chemotherapy sensitivity; the association between different genotypes and chemotherapy sensitivity was analysed. RESULTS: ORR of 67 patients with advanced gastric cancer was 38.8%; CYP3A4*2(+), CYP3A4*3(+), and CYP3A4*4(+) genotype patients accounted for 23.9%, 28.4%, and 26.9% respectively. ORR of patients with CYP3A4*3(+)and CPY3A4*3(-)genotype were 57.9% and 31.3%, with statistical significance (P=0.044); this genotype was associated with chemotherapy sensitivity [OR=3.731, 95%CI(0.901,15.897)]. ORR of patients with CYP3A4*2(+)and CYP3A4*2(-)genotype were 43.7% and 37.3%, without statistical significance (P=0.642); this genotype was not associated with chemotherapy sensitivity [OR=1.075, 95%CI(0.274,16.289)]. ORR of patients with CYP3A4*4(+)and CYP3A4*4(-)were 33.3% and 40.8%, without statistical significance (P=0.577); this genotype was not associated with chemotherapy sensitivity [OR=0.938, 95%CI(0.735,14.732)]. CONCLUSIONS: CYP3A4*3 gene polymorphism may become a biomarker for predicting the sensitivity in advance gastric cancer patients to paclitaxel chemotherapy.