Condyloma acuminatum (CA) is a benign epithelial tumor caused by infection with human papillomaviruses (HPVs) and characterized by abnormal cell proliferation. Cellular caspase-8 (FLICE)-like inhibitory protein (c-FLIP) was originally identified as an inhibitor of death-receptor signaling through competition with caspase-8 for recruitment to FAS-associated via death domain (FADD). More recently, it has been determined that c-FLIP is associated with the survival and proliferation of T cells and keratinocytes. The aim of this work was to study the expression of c-FLIP in CA and its relationship with keratinocyte proliferation. Immunoperoxidase staining methods were applied to analyze the location and expressions of both c-FLIP and proliferating cell nuclear antigens (PCNA) in 34 CA and 16 normal foreskin tissues. Semiquantitative reverse transcriptase-polymerase chain reactions (RT-PCR) and western blotting were performed to further identify the expression of c-FLIP in CA. c-FLIP expression at both mRNA and protein level was significantly higher in CA than normal foreskin. c-FLIP expression was highly correlated with the PCNA labeling index (LI) in CA. We concluded that c-FLIP overexpression might take part in keratinocyte proliferation in CA.