Matrine, a main active component extracted from dry roots of Sophora flavecens , has been reported to exertantitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. Todetermine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays wereemployed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells followingstaining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determinedexpression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNAprofiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and timedependentmanner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reductionin the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared withuntreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing usefulinformation for understanding anticancer mechanisms.