Abstract: Apatinib mesylate is a novel small molecule monoclonal antibody. Its mechanism of action is through highly selective competition for intracellular vascular endothelial growth factor receptor-2 (VEGFR-2) ATP binding sites and blocking downstream signal transduction thereby inhibiting neovascularization of tumor tissue. Hand-foot skin reaction (HFSR) is one of the common adverse reactions of apatinib, and it often affects the quality of life of patients; this leads to a reduction in the use of targeted drugs, which negatively affects the efficacy of anti-tumor therapy. The conventional western medicine treatment for HFSR comprises urea and glucocorticoid topical preparations. Clinical treatment is often based on redness, ulceration, scab, and other skin manifestations; a combination of Chinese and western medicines can improve clinical outcomes. This article reviews apatinib-related HFSR and the relevant progress in treatment strategies in order to provide a clinical reference.