Objective To investigate the expression and significance of TLR4, TLR9 and DC-SIGN in primary and recurrent condyloma acuminatum (CA) lesions. Methods An immunohistochemical method using streptavidin-peroxidase (SP) was performed to detect the expressions and distribution of TLR4, TLR9 and DC-SIGN in tissue specimens obtained from the recurrent CA lesions of 30 patients, primary CA lesions of 30 patients, and from the foreskin of 20 normal human controls. Results The expression levels of TLR4, TLR9 and DC-SIGN in primary and recurrent CA lesions were significantly higher than those in normal control tissue (all P < 0.001), and the cells expressing TLR4, TLR9 or DC-SIGN were mainly located in the basal and spinous layer in CA lesions. There was no significant difference in the expressions of TLR4, TLR9 or DC-SIGN between primary and recurrent CA lesions (all P> 0.05). A positive correlation was found between the expression of TLR4, TLR9 and DC-SIGN in CA lesions. Conclusion The overexpression of TLR4, TLR9 and DC-SIGN probably plays an important role in the occurrence and recurrence of CA.