We first evaluated six ESCC cell lines and two established ESCC PDXs for their in vitro and in vivo sensitivity to the first-, second-, and third-generation EGFR-TKIs (namely gefitinib, afatinib, and osimertinib, respectively) and two EGFR-mAbs (cetuximab and nimotuzumab), respectively. Here, EGFR is linked to esophageal squamous cell carcinoma.