Abstract: To investigate the effect of the IQ domain of GTPase-activating proteins ( IQGAP1 ) on the proliferation of hepatic carcinoma cells and the mTOR signal transduction pathway, and to explain the mechanism of cell proliferation. Methods: The IQGAP1 expression in HepG2 and Huh-7 cells were detected using Western blot analysis. IQGAP1 siRNA was synthesized according to the mRNA sequence of the human IQGAP1 gene and was transfected into HepG2 cells. The effects of IQGAP1 on HepG2 proliferation was analyzed by MTT assay. The effect of IQGAP1 on the cell cycle was analyzed by flow cytometry. The expression levels of IQGAP1, mTOR, and p-mTOR were measured through Western blot analysis. Results: The HepG2 and Huh-7 cells showed detectable levels of IQGAP1, whereas the HepG2 cell line showed higher expression than that in the Huh-7 cells. IQGAP1 siRNA not only inhibited cell proliferation but also increased the number of cells in the G0/G1 phase, with a concomitant decrease in the number of cells in the S phase of the cell cycle. mTOR expression did not significantly change, whereas IQGAP1 and p-mTOR expression were downregulated. Conclusion: These findings suggest that IQGAP1 promotes the proliferation of HepG2 cells, the mechanisms of which may be related to the mTOR pathways.