The innate immune system recognizes conserved features of viral and microbial pathogens via pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are one type of PRRs used by the innate immune system to mediate the secretion of pro-inflammatory cytokines and promote innate and adaptive immune responses. TLR family members TLR7 and TLR8 (refer as TLR7/8 subsequent) are endosomal transmembrane receptors that recognize purine-rich single-stranded RNA and bacterial DNA and thereby elicit an immunologic reaction to pathogens. TLR7/8 have been demonstrated to mediate pro-inflammatory cytokine secretion by activating immune cells. Accumulating evidence indicate that TLR7/8 are closely related to numerous immune-mediated disorders, specifically cancers, autoimmune diseases, and viral diseases. The TLR7/8 agonists and antagonist used as drugs or adjuvants have been well identified in preclinical studies and clinical trials as promising immunostimulators for the immunotherapy of these immune-mediated disorders. These achievements are a good reason for humans to open new doors for exploring immunotherapy of immune-mediated disorders. Nevertheless, many needs remain unmet, and their therapeutic effects are poor, and always cause strong immune-related toxicities. In this mini review, we present an overview of the TLR family members, particularly TLR7/8, and address the underlying molecular mechanisms and clinical implications of TLR7/8 in immune-mediated disorders.