Abstract: Objective To investigate the effect of imiquimod on the proliferation and telomerase activity of human skin squamous cell carcinoma cell line SCL-1. Methods Various concentrations of imiquimod was used to treat cultured SCL-1 cells in log phase. After 48 hours of culture, MTT assay and clonogenic assay were used to assess the proliferation of cells, the morphological alterations were observed by transmission electron microscopy, and telomerase activity was detected with telomeric repeat amplification protocol enzyme-linked immunoadsorbent assay （TRAP-ELISA）. The protein and mRNA expressions of c-Myc were analyzed by immunohistochemistry and real time quantitative RT-PCR, respectively. Results The 48-hour treatment with imiquimod at the concentrations of 0.05, 0.10, 0.15 and 0.20 g/L down-regulated the proliferation of SCL-1 cells by 31.3% ± 3.19%, 44.7% ± 4.21%, 49.2% ± 3.71% and 71.6% ± 3.24%, respectively, and telomerase activity of SCL-1 cells was also inhibited by imiquimod; both effects were concentration-dependant. A reduction in mRNA and protein expressions of c-Myc was observed in SCL-1 cells after the treatment with imiquimod at 0.05 and 0.15 g/L, respectively （both P < 0.05）. Conclusion Imiquimod can effectively inhibit the proliferation and telomerase activity of SCL-1 cells, decrease the expression of c-Myc gene, which may be associated with the mechanism of antitumor effect of imiquimod.