Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal carcinoma in China. The overall 5-year survival rate of ESCC patients is in the low range of 15-25%. One important reason for the poor prognosis is that the underlying molecular mechanisms are unclear. Furthermore, the development of effective therapeutic strategies to improve patient outcome is needed. Animal models can be beneficial to analyze the molecular mechanisms as well as specific clinical therapeutic strategies for esophageal cancer. In recent years, patient-derived xenografts (PDXs) have been widely used in numerous types of cancers to investigate the basic mechanisms and to conduct preclinical research. Accumulating evidence indicates that the PDX model is an important tool for basic and clinical research. Herein, we successfully established 14 ESCC PDXs. These PDX models preserved the patient pathological characteristics and effectively reflected the patient biological heterogeneity. Cancers exhibit diverse growth rates and tumor texture, even more, they have different signaling pathways. The PDX model is a superior strategy for understanding the underlying molecular mechanisms of ESCC and for screening new therapeutic strategies for ESCC patients.