Abstract: Objective To investigate the interaction of fibronectin and paxillin in human gastric cancer cell, AGS, and reversal effects of paxillin siRNA on invasiveness of AGS cell induced by fibronectin. Methods A gastric cancer cell line, AGS, was stimulated by fibronectin with gradient concentrations (0, 10, 100, 1 000nmol/L). The phosphorylation expression of paxillin tyrosine 118（tyr-118）, was detected by immunoprecipitation and Western blot. The invasiveness of AGS cells was measured by the modified Boyden chamber assay. siRNA targeting paxillin was transfected into AGS cells, effect of paxillin silencing on phosphorylation of paxillin (tyr--118) and invasiveness of AGS cells stimulated by fibronectin were detected respectively. Results The AGS cell showed a dose-dependence on fibronectin in phosphorylation of paxillin tyr-118 and its invasiveness. Invasiveness and phosphorylation of paxillin tyr-118 in AGS reached their climax when the concentration of fibronectin reached 100nmol/L, whereas the expression of paxillin remained unchanged after stimulated by fibronectin（P>0.05）. siRNA targeting paxillin suppressed phosphorylation of paxillin tyr-118 and the invasiveness of AGS cells significantly,decreased compared with the controls（P<0.05）. Conclusion Fibronectin promotes paxillin tyr-118 phosphorylation and invasiveness of AGS cells. Paxillin silenced by RNA interference inhibits the cell invasiveness stimulated by fibronectin. Paxillin is a key factor in the fibronectin-stimulated cell invasiveness of AGS cells.