Objective: To investigate the short-term efficacy of apatinib combined with tegio in the treatment of stage III–IV gastric cancer and the effect on the levels of carcino embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9). Methods: Eighty patients with stage III–IV gastric cancer who failed in the first-line treatment during from March 1, 2015 to December 31, 2018 in the Department of Oncology of Chizhou People’s Hospital were randomly divided into single drug group and combined group with 40 cases in each group. On the basis of routine treatment, all patients with stage III–IV gastric cancer were treated with tegio alone in the single drug group and apatinib combined with tegio in the combined group, all of which lasted for 3 weeks/chemotherapy cycle and 2–3 chemotherapy cycles.Response evaluation criteria in solid tumors (RECIST) was used to compare the response rate (RR) and the disease control rate (DCR) of the two groups. CEA and CA19-9 levels of serum tumor markers before treatment were measured. The World Health Organization criteria for the toxicity of anticancer drugs (0–IV degree) was used to evaluate them To evaluate the side effects of the two groups during the treatment. Results: The RR and DCR of the combination group were 32.50% and 77.50%, respectively, and the RR and DCR of the single drug group were 22.50% and 55.00%, respectively. The DCR of the combination group was significantly higher than that of the single drug group, the difference was statistically significant (P<0.05). There was no significant change in serum CEA and CA19-9 levels before and after treatment in the single drug group (P>0.05), but the serum CEA and CA19-9 levels in the combined group decreased significantly (P<0.05), which was also significantly lower than that in the single drug group, the difference was statistically significant (P<0.05); there was no significant difference in the incidence of nausea and vomiting, diarrhea and abdominal pain, asthenia, leukopenia, thrombocytopenia, liver enzyme abnormality, electrolyte abnormality, rash and HFS between the two groups (all P>0.05), the incidence of upper gastrointestinal hemorrhage and oral mucositis in the combined group was higher than that in the single drug group (all P<0.05). Conclusion: apatinib combined with second-line treatment of tegio can effectively control the progression of gastric cancer, reduce the level of serum CEA and CA19-9, and the side effects are mainly I–II degree. The patients have good tolerance and significant clinical application value.