Abstract:ObjectiveTo explore the clinical efficacy, safety, serum tumor markers and vascular endothelial growth factor (VEGF) levels of low-dose apatinib combined with second-line chemotherapy in patients with advanced gastric cancer. Methods A total of fifty patients with advanced gastric cancer who were diagnosed in the First Affiliated Hospital of Bengbu Medical College from January 2019 to December 2020 after first-line platinum-containing chemotherapy were selected. According to whether the second-line treatment plan used apatinib or not, they were divided into two groups. The observation grouPwas treated with low-dose apatinib combined with albumin-bound paclitaxel or docetaxel, and the control grouPwas treated with pure albumin-bound paclitaxel or docetaxel, 21 days as a treatment cycle. The clinical efficacy, adverse reactions, tumor markers（CEA、CA19-9、CA724） and VEGF levels were observed between two groups. Results The objective response rate (ORR) of the observation grouPand the control grouPwere 20.0% and 12.0%, respectively, which were not statistically significant (P＞0.05). The disease control rate (DCR) was 76.0% and 48.0%, and the median progression-free survival (mPFS) was 4.8 months (95% CI ：4.2-5.5) and 3.5 months (95% CI ：3.3-4.4), respectively, and there were statistical differences between the two groups (P<0.05). The incidence of hypertension and hand-foot syndrome in the observation grouPwas higher than that in the control grouP (P<0.05), but there was no significant difference in other adverse reactions (P＞0.05). After treatment, the serum levels of CEA, CA19-9, CA724 and VEGF in two groups were decreased (P<0.05), and the decrease was more obvious in observation grouPcompared with control grouP(P<0.05). Conclusions Low-dose apatinib combined with second-line chemotherapy in the treatment of patients with advanced gastric cancer can improve the clinical efficacy, safe tolerance, and significantly reduce serum tumor markers and VEGF levels.