Objective To investigate the effect of siomycin A-induced forkhead box protein M1(FoxM1) down-regulation on the malignant behaviors (proliferation, apoptosis, and invasive ability) of laryngeal carcinoma cells. Methods The experiment was performed with Hep-2 cells of the logarithmic growth phase. The experimental groups were treated with different doses of siomycin A, and the control group was treated without siomycin A. CCK-8 test was used to detect the viability of Hep-2 cells after treatment for 24, 48, and 72 h. CFSE staining was used to examine the proliferation ability of Hep-2 cells after treatment for 24 and 48 h. Annexin Ⅴ-FITC/PI dual staining was used to observe the siomycin A-induced apoptosis and Transwell test was used to examine the invasion ability of Hep-2 cells after treatment for 48 h. The expressions of FoxM1, Ki-67 and cleaved caspase-3 protein in Hep-2 cells were detected by Western blotting analysis. The supernatant levels of matrix metalloproteinase (MMP)-2 and MMP-9 were examined by ELISA assay. Results (1) Treatment with siomycin A significantly decreased the expression of FoxM1 protein compared with the control group (P<0.05). CCK-8 test found that siomycin A of different concentrations suppressed the viability of Hep-2 cells in a time- and dose-dependent manner. (2) Siomycin A at 1.3 and 1.5 μmol/L significantly suppressed the proliferation of Hep-2 cells in a dose-dependent manner (P<0.05), accompanied by down-regulated expression of Ki-67.(3)Siomycin A at 1.3 and 1.5 μmol/L also induced greater apoptosis of Hep-2 cells (10.6%, 27.9 %) in a dose-dependent manner compared with control group (4.91%, P<0.05), accompanied by up-regulated cleaved caspase-3 expression. (4) Siomycin A at 1.3 and 1.5 μmol/L suppressed the invasive ability of Hep-2 cells in a dose-dependent manner compared with control group (P<0.05), accompanied by down-regulated expression of MMP-2 and MMP-9. Conclusion Down-regulation of FoxM1 by siomycin A can inhibit the proliferation and invasive ability of laryngeal carcinoma cells.