Background: Warts are prevalent human papilloma virus (HPV) infections which can cause physical and psychological problems. Candida antigen immunotherapy is a safe and promising treatment of warts. Toll-like receptors (TLRs) 2 and 4 gene polymorphisms are implicated in susceptibility and progression of several diseases. Aim: To assess the role of TLR2Arg753GLN and TLR4Asp299Gly polymorphisms in susceptibility to HPV wart infections and their possible effect on response to Candida antigen immunotherapy. Patients and methods: A total of 78 patients and 78 healthy subjects were enrolled in this case control study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect TLR2Arg753GLN and TLR4Asp299Gly genes polymorphisms. Patients’ lesions were injected with Candida antigens and the response was assessed. Results: The mutant AA and GG genotypes of TLR2Arg753GLN and TLR4Asp299Gly were significantly detected in patients than controls (p < .001 and p ¼ .01, respectively). Intralesional Candida antigen injections achieved complete and partial clearance in 62.8 and 20.5% of lesions, respectively. No association was found between the studied polymorphisms and response to Candida antigen injections. Conclusions: TLR2Arg753GLN and TLR4Asp299Gly polymorphisms are associated with susceptibility to wart infections, but with no effect on their response to Candida immunotherapy.