Objective To observe the inhibitory effect of matrine on K-ras gene mutation colon cancer, and to clarify the inhibitory mechanism. Methods SW480 cells were treated with different concentrations of matrine. MTS method was used to detect the proliferation of SW480 cell lines. The apoptosis of SW480 cells was measured by flow cytometry. The migration of SW480 cells was examined by the scratch test. The expression of MEK1/2 protein was detected by Western blotting method. Results Compared with the blank control group, matrine (0.125-1 mg/mL) could inhibit the growth and proliferation of human colorectal cancer SW480 cell lines, promote the apoptosis, restrain the migration of SW480 cells, and inhibit the expression of MEK1/2 protein(P < 0.05), the effect showing a dose-dependent trend. Conclusion Matrine can effectively inhibit the proliferation and migration of SW480 cells, and promote SW480 cell apoptosis through the down-regulation of MEK1/2 protein expression in MAPK signal pathway system.