Abstract： Objective To investigate the expression of EGFR, Her-2 and TOPO Ⅱ in esophageal canceration course, analyze the correlation between the expression and clinical pathological parameters and the correlation of the three genes. Methods EGFR, Her-2 and TOPO Ⅱ were detected by Tissue microarray technology and Envision immunohistochemistry method in 107 cases of esophageal carcinoma, including normal esophageal epithelium, esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma. Results The positive expression rates of EGFR and TOPO Ⅱ display an improving trend from normal esophageal epithelium, intraepithelial neoplasia to carcinoma (P =0.031) in the above four groups. The positive expression rates of EGFR were 8.41 %, 7.94 %, 27.27 %, 50.47 %, and TOPO Ⅱ were 3.74 %, 4.76 %, 20.45 %, 43.93 %. Furthermore, the expression showed gradually incresing with histological grades advance (P =0.009). There was no correlation between EGFR or TOPO Ⅱ and gender, age, lymph node or distant metastasis (P >0.05). There was a positive correlation between EGFR and TOPO Ⅱ (r 1=0.410, P <0.05). There were no significance of Her-2 protein expression among the three groups(P >0.05), no correlation was obtained between Her-2 and gender, age, the depth of invasion or lymph node metastasis (P >0.05), no relationship between Her-2 and EGFR or TOPO Ⅱ either. Conclusion EGFR and TOPO Ⅱ are closely related to the occurrence and development of esophageal squamous cell carcinoma, their expressions all make a qualitative change in the esophageal high-grade intraepithelial neoplasia. The role of Her-2 in the development of esophageal squamous cell carcinoma is still not definite in Shanxi province.