Objective To study the mechanism of matrine inhibiting human colon cancer cells through the IL-6/STAT3 signaling pathway. MethodHuman colon cancer cell HCT-116 was interfered with matrine, cell proliferation assay CCK-8 was used to detect cell proliferation, and the protein expression level of inflammatory factor IL-6/STAT3 gene and the protein expression level of metastatic power of colon cancer cell E-CAD gene were detected by Western blot assay. Results The cell proliferation test showed that the cell proliferation of 2mg/mL, 3mg/mL and 4mg/mL matrine groups was significantly lower than that of the control group. Western blot results showed that the matrine group had IL-6 / STAT3 protein compared with the control The expression level was significantly decreased (P<0.05), and the expression level of E-Cad protein was significantly increased(P<0.05). Conclusion Matrine can reduce the inflammatory response of human colon cancer cell HCT-116 by inhibiting IL-6/STAT3 signaling pathway, and further inhibit the proliferation and invasiveness of human colon cancer cell HCT-116, so as to achieve anti-tumor effect.