Objective To explore the expression of YKL-40 and vascular endothelial cell growth factor (VEGF) in condyloma acuminatum (CA) tissues and the related significance. Methods The expressions of YKL-40 and VEGF were analyzed by immunocytochemical staining with streptavidin-peroxidase (SP) in 33 CA tissues and 10 foreskin tissues of normal person. Results The expression intensities of YKL-40 and VEGF varied largely from positive () to strongly positive () in CA tissues compared with negative (-) and positive (+) in normal foreskin tissues. The expressions of YKL-40 and VEGF proteins in CA tissues were significantly different from those in the normal human controls(P<0.05). No correlation was found between the expression of YKL-40 and VEGF proteins in CA tissues (r=0.27, P>0.05), and their expressions were not correlated with other clinical factors (P>0.05). Conclusion YKL-40 and VEGF are over-expressed in CA tissues, which may play a part in the occurrence and development of CA.