Drug-induced liver injury (DILI) with extrahepatic adverse drug reaction (EHADR) is the injury of extrahepatic organs which is caused by the same drug inducing liver injury and may occur simultaneously or successively with DILI, such as the skin, gastrointestinal tract, blood system, cardiovascular system, and bone and joint system, and it should be taken seriously in clinical practice. DILI with EHADR is not rare, and its pathogenesis may be associated with various factors including the physicochemical properties, distribution, metabolism, excretion, biological activity, and immunological properties of drugs, host genetic background, and underlying diseases. The diagnosis and treatment of DILI with EHADR is more challenging than that of DILI alone.