Abstract: The human epidermal growth factor receptor inhibitors(EGFRIs) are the most widely used molecular targeted therapy drugs in cancer field at present. The representative drugs includes gifetinib, erlotinib, and ectatinib. While EGFRIs achieve efficacy, the adverse skin reactions brought to the patients by them can not be ignored. In severe cases, they can affect the dose of cancer patients and even interrupt treatment. This paper reviews the clinical manifestation and mechanism of adverse skin reactions caused by EGFRIs, including alterations of keratinocyte proliferation, differentiation and apoptosis, enhanced inflammatory response and photosensitivity to ultraviolet radiation. It is expected that these mechanism studies will provide new treatment ideas to reduce the adverse drug reaction, improve the patient drug compliance and improve the efficacy on tumor.