Therapeutic approaches that increase the efficacy and safety of cancer treatments and improve disease outcomes have been developed worldwide. Immunotherapy uses the body's immune system to inhibit cancerous growth in tissues and organs. Various approaches have been developed to effectively control and inhibit cancerous growth, including checkpoint inhibitors, T-cell transfer therapy, monoclonal antibodies, vaccines and immunomodulators. Toll-like receptors (TLRs) target malignant cells by equipping the immune response. In addition, TLR agonists serve a key role in promoting the innate immune system and initiating antigen-specific T-cell responses. Notably, TLRs and TLR agonists have been utilized as monotherapies or in combination for the treatment of cancer. The present study aimed to review the use of R848 and R837 as TLR agonists, and outline their use as key immunomodulators in cancer therapy.