Purpose: To investigate the effect of apatinib combined with chemotherapy on quality of life (QOL) and related complications in patients with advanced gastric cancer (AGC). Methods: Clinical data for 102 AGC patients treated in The Affiliated Hospital of Hebei University (January 2018 - December 2019) were retrospectively analyzed. The subjects were randomly and equally split into chemotherapy group and combination group. Both groups of patients were treated with 180 mg/m2 of paclitacel, and patients in the combination group were additionally given 500 mg of apatinib daily, for a treatment time to disease remission in both groups. Clinical efficacy, QOL, complications as well as serum SIL-2R, VEGF and TNF-alpha levels in the two groups were compared to analyze the effect of apatinib combined with chemotherapy on AGC patients. Results: Disease control rate (DCR) and overall response rate (ORR) of gastric cancer patients in the combination group were notably higher than those in the chemotherapy group (p < 0.05). After treatment, the serum SIL-2R, VEGF and TNF-alpha levels in the two groups decreased significantly, of which the levels in the combination group were clearly lower (p < 0.05). No notable difference in the incidence of complications was observed between the two groups (p > 0.05). After treatment, the QOL scores of both groups increased significantly, of which QOL score in the combination group was notably higher (p < 0.05). Conclusion: Apatinib combined with chemotherapy effectively enhances the clinical efficacy of AGC patients, controls the overexpression of serum SIL-2R, VEGF and TNF-alpha, and improves the QOL of patients without increasing adverse reactions. Therefore, the combination therapy is safe and effective.