Quercetin, a wild distributed bioflavonoid, exhibits antitumor effects on murine models by inducing apoptosis and inhibiting growth of many cancer cell lines, while proteins involved in antitumor effects at proteomic level are still unclear. In our study, we used a quantitative proteomic strategy termed stable isotope labeling by amino acids in cell culture (SILAC)-mass spectrometry (MS) to study the differential proteomic profiling of HepG2 cells treated by quercetin. In all, there were 70 changed proteins among those quantified proteins in HepG2 cells treated by 50 mu M quercetin for 48 h, and 14 proteins showed significant upregulation, whereas 56 proteins were downregulated. The functional classification of changed proteins includes signaling protein, protein synthesis, cytoskeleton, metabolism, etc. Of these, Ras GTPase-activating-like protein (IQGAP1) and beta-tubulin were found to be reduced at a large degree. The migration inhibition of HepG2 cells can be induced by quercetin, and the RNA and protein expression level of IQGAP1 and beta-tubulin were respectively decreased obviously in HepG2 cells exposed to quercetin for 48 h in the scratch migration assay. The downregulated expression of IQGAP1 and beta-tubulin by quercetin treatment correlated with cell migration ability, and quercetin probably inhibits HepG2 proliferation and migration through IQGAP1 and beta-tubulin expression changes and their interactions with other proteins.