The purpose of this study was to explore the relationship between the expression of vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER-2), and epidermal growth factor receptor (EGFR) mRNA in esophageal squamous cell carcinoma (ESCC) and the clinicopathological characteristics of the Han, Uyghur, and Kazakh in Xinjiang. Real-time quantitative polymerase chain reaction technology (RT-PCR) was used to detect the expression of VEGF, HER-2, and EGFR mRNA in esophageal squamous cancer tissue of 60 cases and 30 cases of VEGF, HER-2, and EGFR mRNA in esophageal cancer adjacent tissues, and analyze its relationship with clinicopathological features. The results were as follows: (1) There was no statistically significant difference in esophageal tissue VEGF, HER-2, and EGFR mRNA gene expression levels of the Han, Uyghur, and Kazakh patients (P > 0.05). (2) The expression levels of VEGF, HER-2, and EGFR mRNA in ESCC group were higher than those in adjacent esophageal tissue group (P < 0.05). (3) The expression levels of VEGF and HER-2 mRNA in ESCC of the Han patients were higher than those of the Uyghur and Kazakh patients (P < 0.05). (4) The expression levels of VEGF, HER-2, and EGFR mRNA in lymph node metastases were higher than those without lymph node metastasis (P < 0.05). (5) The expression level of HER-2 mRNA was related with the degrees of pathological differentiation, and the higher pathologic degree, the lower expression level in HER-2 mRNA (P < 0.05). Therefore, the following conclusions were drawn: (1) There were ethnic differences in the VEGF and HER-2 gene mRNA expression levels of the Uyghur, Han, and Kazakh patients in Xinjiang. (2) The expressions of VEGF, HER-2, and EGFR mRNA were related to the lymph node metastasis in ESCC and pathologic differentiation degree.