Objective To investigate supportive therapeutic efficacy of hyperthermia in patients with esophageal cancer and its effect on the level of serum carbohydrate antigen 199 (CA199) and vascular endothelial growth factor (VEGF). Methods Included in the study were 100 patients with esophageal cancer who attended the Department of Thoracic Surgery of Baoji People′s Hospital from September 2012 to September 2016. They were randomized into hyperthermia group and control group, with 50 cases in each group. The control group was given chemotherapy with docetaxel+nedaplatin and conventional radiotherapy, and the hyperthermia group were given hyperthermia in addition to the treatment for the control group. The two groups were compared in the level of serum CA199, VEGF and therapeutic efficacy, adverse reactions, and survival rates. SPSS statistics 22.0 was used for data analysis. Depending on data type, Student′s t test, Chi-square test or rank-sum test was used for comparison between groups, the paired t-test for comparison within the group, and Kaplan-Meier curve analysis for survival prognosis. Results The efficacy was higher in the hyperthermia group than in the control group, with significant difference [90.00%(45/50) vs 74.00%(37/50), P=0.04]. The serum level of CA199 and VEGF in both groups were significantly lower after treatment than those before treatment, and the serum level of CA199 [(50.42±5.54) vs (76.45±7.72)U/ml] and VEGF [(137.2±15.5) vs (203.5±24.0)pg/ml] after treatment were significantly lower in the hyperthermia group than those in the control group, the differences being statistically significant (P<0.01). No statistically significant difference was observed in the incidence of adverse reactions between the two groups (P=0.46). During 2-year follow-up, the survival rate in the hyperthermia group was significantly higher than that in control group [60.00%(30/50) vs 40.00%(20/50), P=0.03]. Conclusion Hyperthermia can effectively enhance the therapeutic efficacy of the conventional chemo-therapy and radiotherapy in esophageal cancer patients with increased survival and satisfactory safety. It is worthy of further promotion in clinical practice.