Human epidermal growth factor receptor-3 (HER-3) is the third member of the HER family. It was previously considered not to contain tyrosine kinase activity and catalytic activity and the intracellular region of HER-3 could not bind ATP and be auto-phosphorylated. Thus, the clinical value of HER-3 was ignored. Currently, biochemical analysis has confirmed that the kinase domain of HER-3 is a specific allosteric activator; it acts as a functional activator to activate the recipient kinase (HER-1, HER-2, HER-4). With the in-depth knowledge of its structure and function, studies on the relationship of HER-3 and human tumors are rapidly increasing. HER-3 is closely related to tumorigenesis, progression and metastasis. HER-3 is involved in resistance to targeted therapy, and may serve as a new therapeutic target. The expression of HER-3 helps to predict prognosis and treatment efficacy. HER-3 has become a focus of concern in the HER family and has gained significant attention in the search for cancer treatment.