Abstract: Objective: To observe the effects of Doxycycline on matrix metalloproteinase - 2 (MMP2) mRNA expression, invasion, and biological activities in the human colorectal cancer cell line LS174T in order to shed light on the molecular mechanism behind Doxycycline's ability to inhibit tumor invasion and metastasis. Methods: a) The effect of Doxycycline on the adhesion activity of LS174T was observed using MTT reduction assay (MTT), and the inhibitory effects on invasion and motility were detected using the Trans- well zeta method. b) RT- PCR was used to detect the mRNA expression of MMP2. At the same, total protein was extracted and used to detect MMP2's gelatinase activity. Results:a) Doxycycline could inhibit the in vitro motility and invasion abilities of the LS174T cells in a dose-dependent manner, with no effect on adhesion. b) Doxycycline could also inhibit the expression of MMP2 mRNA. Conclusion: Doxycycline can effectively inhibit the growth, invasion and metastasis of the LS174T colorectal cancer cells in vitro by inhibiting mRNA expression of MMP2.