Objective To study the relationship between circular RNA SH3 binding protein 1(circSHKBP1),SRY-box transcription factor 3(SOX3)and chemotherapy efficacy and prognosis in patients with advanced gastric cancer.Meth-ods A total of 104 patients with advanced gastric cancer admitted to the Department of Oncology,Tangdu Hospital of Air Force Medical University from January 2019 to February 2021 were selected as the study group,and they were divided into chemotherapy-sensitive subgroup and chemotherapy-resistant subgroup according to the efficacy of chemotherapy;50 healthy subjects were selected as healthy control group.Real-time fluorescence quantitative PCR was used to detect the levels of serum circSHKBP1 and SOX3 mRNA in each group;the relationship between serum circSHKBP1,SOX3 mRNA ex-pression and clinicopathological features of patients with advanced gastric cancer was analyzed.Multivariate Logistic re-gression analysis was used to analyze the factors affecting the efficacy of chemotherapy.The receiver operating characteris-tic curve was used to analyze the value of serum circSHKBP1 and SOX3 mRNA in evaluating the efficacy of chemotherapy in patients with advanced gastric cancer.Results The relative expression levels of serum circSHKBP1 and SOX3 mRNA in the study group were(3 22±0.37)and(2.72±035),respectively,which were higher than those in the control group(0.62±0.17),(0.71±0.19),(t=65.118,51.471,both P<0.001).The relative expression levels of serum circSHKBP1 and SOX3 mRNA in patients with TNM stage Ⅳ and poorly differentiated advanced gastric cancer were higher than those in patients with TNM stage ⅢB and high and medium differentiation(t/P=37.283/<0.001,31.545/<0.001,19.169/<0.001,26.334/<0.001).The per-centage of tumor stage Ⅳ in the chemotherapy-resistant subgroup and the relative expression of serum circSHKBP1 and SOX3 mRNA were higher than those in the chemotherapy-sensitive subgroup(t/P=10.037/0.002,48.609/<0.001,26.775/<0.001).Tumor stage Ⅳ,serum circSHKBP1 and SOX3 mRNA were risk factors for chemotherapy resistance in advanced gas-tric cancer[HR(5%CI)=1.594(1.252-2.028),1.306(1.144-1.492),1.603(1.190-2.160)];The AUC of circSHKBP1,SOX3 mRNA and the combination of the two in predicting the efficacy of chemotherapy in patients with gastric cancer were 0.844,0.851 and 0.922,respectively.The combination of the two was superior to their respective predictive efficacy(Z=4.745,4.310,P<0.001).Conclusion The serum levels of circSHKBP1 and SOX3 mRNA in advanced gastric cancer are increased,which are related to the degree of tumor differentiation,TNM stage and chemotherapy efficacy.The combination of the two has a good evaluation value for the chemotherapy efficacy of patients with advanced gastric cancer.