Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that play a crucial role in the regulation of host protective adaptive immune responses. They recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), triggering downstream signaling pathways that initiate innate and adaptive immune responses. Inappropriate TLR stimulation can lead to autoimmune diseases, chronic and acute inflammation, and cancer. This review summarizes recent discoveries in the molecular and structural biology of TLRs, highlighting their roles in various inflammatory and autoimmune diseases, as well as their potential as therapeutic targets. The article discusses the signaling pathways activated by different TLRs, including the MyD88-dependent and TRIF-dependent pathways, and their involvement in diseases such as respiratory, cardiovascular, digestive, endocrine, and sepsis. It also explores the relationship between TLRs and carcinogenesis, particularly in oral squamous cell carcinoma, breast cancer, colorectal cancer, gastric cancer, and other malignancies. The review concludes by discussing the potential of TLRs as therapeutic targets for various diseases, emphasizing the need for further research to optimize their use in clinical settings.Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that play a crucial role in the regulation of host protective adaptive immune responses. They recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), triggering downstream signaling pathways that initiate innate and adaptive immune responses. Inappropriate TLR stimulation can lead to autoimmune diseases, chronic and acute inflammation, and cancer. This review summarizes recent discoveries in the molecular and structural biology of TLRs, highlighting their roles in various inflammatory and autoimmune diseases, as well as their potential as therapeutic targets. The article discusses the signaling pathways activated by different TLRs, including the MyD88-dependent and TRIF-dependent pathways, and their involvement in diseases such as respiratory, cardiovascular, digestive, endocrine, and sepsis. It also explores the relationship between TLRs and carcinogenesis, particularly in oral squamous cell carcinoma, breast cancer, colorectal cancer, gastric cancer, and other malignancies. The review concludes by discussing the potential of TLRs as therapeutic targets for various diseases, emphasizing the need for further research to optimize their use in clinical settings.