The incidence and mortality of esophageal cancer in China rank the fifth and fourth, respectively, with squamous carcinoma accounting for more than 90%. Currently, the treatment of esophageal squamous carcinoma mainly includes surgery, chemotherapy, radiotherapy, and endoscopic treatment. However, the 5-year survival rate is only about 20%. At present, the treatment of esophageal squamous carcinoma seems to reach a plateau. Thus, it is urgent to develop new and more effective drugs and treatments. In this paper, the clinical research progresses of epidermal growth factor receptor (EGFR)- targeted therapy of esophageal squamous carcinomas were summarized, including anti-EGFR monoclonal antibodies, such as cetuximab and nimotuzumab, and EGFR-tyrosine kinase inhibitor, such as gefitinib, erlotinib, and ecclinib.