Abstract： AIM To observe the curative effect and side effects of capecitabine metronomic chemotherapy combined with three-dimensional conformal radiotherapy in patients with advanced esophageal cancer and the effect on serum tumor markers, vascular endothelial growth factor (VEGF), C-reactive protein (CRP), and matrix metalloproteinases. METHODS The clinical data of 130 elderly patients with esophageal cancer admitted to our hospital from April 2011 to April 2016 were retrospectively analyzed. Among them, 60 patients received the PFchemotherapy regimen (PDD 75 mg/m2, dl, 5-Fu 1 g/m2, dl-d4; one course of chemotherapy for every 28 d, two courses in total) combined with three-dimensional conformal radiotherapy (control group), and the other 70 patients were given metronomic chemotherapy (0.6 g/m2, bid, oral administration after breakfast and dinner, one course of chemotherapy for every 28 d, two courses in total) combined with three-dimensional conformal radiotherapy (observation group). Clinical efficacy, adverse reactions, serum tumor markers, VEGF, CRP, matrix metalloproteinases, and other indicators were compared in the two groups of patients. RESULTS The total effective rate was significantly higher in the observation group than in the control group (82.86％ vs 65.0％, P ＜ 0.05). Before treatment, there was no significant difference in the levels of CA125, CA19-9, CEA, VEGF, CRP, MMP-2, or MMP-9 between the two groups (P ＞ 0.05). After treatment, the levels of CA125, CA19-9, CEA, VEGF, CRP, MMP-2, and MMP-9 in the observation group were significantly lower than those in the control group (8.05±2.32 vs 9.76±2.35, 7.06±6.61 vs 9.22±8.58, 1.39±0.39 vs 1.89±0.46, 259.25±21.21 vs 352.28±30.37, 6.25±0.16 vs 9.08±0.22, 65.05±1.71 vs 91.12±2.01, 297.06±146.61 vs 492.22±158.58, P ＜ 0.05). The incidence rates of leukopenia, digestive tract reactions, and liver dysfunction were significantly lower in the observation group than in the control group (15.71％ vs 35.0％, 27.14％ vs 51.67％, 18.57％ vs36.67％, P ＜ 0.05). CONCLUSION Capecitabine metronomic chemotherapy in combination with three-dimensional conformal radiotherapy in elderly patients with esophageal cancer can significantly improve clinical efficacy and effectively reduce serum tumor markers, VEGF, CRP, and matrix metalloproteinases with high safety.