Recent studies indicate that several Toll-like receptors (TLRs) areimplicated in recognizing viral structures and instigating immune responses against viral infections. Warts are benign proliferations of skin and mucosa caused by the human papillomavirus (HPV). The effect of cryotherapy on wart clearance may be through necrotic destruction of HPV-infected keratinocytes or by inducing local inflammation that triggers an effective cell-mediated response The aim of this study is to detect the expression of TLR 9 in verruca vulgaris & the possible changes that may occur in TLR 9 expression in adjacent warts after treating one of them. Polymerase chain reaction (PCR) and In-situ PCR of skin samples were performed to determine the expression and localization of mRNA of TLR 9. In normal human skin, the level of TLR9 was low. In veruuca vulgaris lesions, the level of TLR9 was very high. After cryotherapy it was but not reach to normal skin level. Likewise, In-situ PCR indicated that keratinocytes of epidermis in NS little expressed TLR9, whereas TLR9 was strongly expressed on the epidermis and dermis of VV lesions. In addition, the mRNAof TLR9 was moderate expression in the VV after cryotherapy. Our results indicated that TLR9 may have an important role in cutaneous innate immune responses to cutaneous human papillomavirus infections and the using of cryocautery in treatment of warts may enhance the immune response against the viral infection.