Objective：This study aims to investigate the effects of adenovirus E1A associated 300 kDa protein（p300） on the migration，invasion and matrix metalloproteinase-2（MMP2） expression in non-small cell lung cancer（NSCLC） cells stimulated by IL-17. Methods：After NSCLC cells（H1299） incubated with IL-17，scratch and transwell experiments were performed to observe the cell migration and invasion. Then the p300 and MMP2 protein expression was detected using Western blot. Meantime，p300 overexpression plasmids（pcDNA3.1/p300） or short hairpin RNA（shp300） plasmids were transfected into H1299 cells（the latter was stimulated with IL-17），respectively，and the cell migration，invasion and MMP2 synthesis were again examined by the same method described above. Results：The migration and invasion as well as the expression of p300 and MMP2 were obviously elevated in H1299 cells treated by IL-17. And p300 overexpression significantly promoted the cell migration，invasion，and MMP2 expression. While p300 gene knockdown by shp300 led to the decrease of migration，invasion and MMP2 production in H1299 cells induced by IL-17. Conclusion：IL-17-upregulates p300 in H1299 cells which enhances the cell migration，invasion and MMP2 expression.