Objective: To investigate the clinical efficacy and safety of Apatinib Mesylate in the treatment of advanced gastric cancer patients who failed second-line chemotherapy. Methods: 80 postoperative patients with advanced gastric cancer who failed second-line chemotherapy were randomly divided into observation group and control group, with 40 cases in each group. The patients in control group were treated with conventional chemotherapy, 2 weeks as a course of treatment and all the patients were treated for 4 courses. The patients in observation group were treated with conventional chemotherapy combined Apatinib Mesylate, 1 week of Apatinib Mesylate was a course of treatment and all the patients were treated 4 courses. After treatment, RECIS solid tumor efficacy evaluation criteria was used to evaluate the clinical efficacy, and adverse reactions were also observed. Results: The total effective rate and disease control rate of patients in the observation group were 50.0% and 90.0% respectively, which were all obviously higher than control group (P<0.05).The incidence of hypertension, vomiting, diarrhea, rash, hand-foot syndrome, stomatitis of patients in observation group were all obviously lower than control group (P<0.05). Conclusions: Apatinib Mesylate combined conventional chemotherapy can obviously improve the curative effects of advanced gastric cancer patients who failed second-line chemotherapy, and the incidence of adverse reactions are lower, so it is worthy of clinical promotion.