Abstract：Objective：To discuss the effect of harmine on proliferation and apoptosis of A549 lung cancer cells as well as its possible mechanism. Methods： The A549 cells were treated with harmine with different concentrations(0.175， 0.35， 0.7 ng/mL) for 24 hours；cell proliferation was detected by cell count kit-8(CCK-8) and colony forming assay；cell apoptosis was detected by flow cytometry；the expression level of protein of proliferating cell nuclear antigen Ki67 and Caspases3 were detected by Western blot；the level of gene expression of FOXD3 Antisense RNA 1(FOXD3-AS1) was detected by real time fluorescence quantitative PCR(RT- qPCR). FOXD3- AS1 siRNA was transfected into A549 cells； after the same treatments mentioned above，the effect of down-regulation of FOXD3-AS1 expression on proliferation and apoptosis of A549 cells and on Caspases3 protein expression was observed. Results：After the treatment of harmine on A549 cells，cell survival rate， colony formation count，and the expression of Ki67 protein and FOXD3-AS1 were decreased(P＜0.05)，but the rate of cell apoptosis and the expression of Caspase3 protein were increased(P＜0.05). After the down- regulation of FOXD3- AS1 expression，the survival rate of A549 cells，colony formation count，and level of Ki67 protein expression were decreased(P＜ 0.05)，but the rate of cell apoptosis and the expression of Caspase3 were increased(P＜0.05). After the down-regulation of FOXD3-AS1 expression and the treatment of harmine on A549 cells，cell survival rate，colony formation count，and level of Ki67 protein expression were decreased(P＜0.05)；the rate of cell apoptosis and level of Caspase3 protein expression were increased(P＜0.05). Conclusion： Harmine may inhibit the proliferation and promote apoptosis of A549 lung cancer cells by down regulating the expression of FOXD3-AS1.