Background: TIAM2, a Rac guanine nucleotide exchange factor, is closely associated with cell adherenceand migration. Here, we aimed to investigate the role of TIAM2 in non-small cell lung cancer (NSCLC) cells.Materials and Methods: A small interference RNA (siRNA) was introduced to silence the expression of TIAM2.Invasion and motility assays were then performed to assess the invasion and motility potential of NSCLC cells.GST-pull down assays were used to detect activation of Rac1. Results: TIAM2 was highly expressed in NSCLCcells. Knockdown of TIAM2 inhibited the invasion and motility, and suppressed activation of Rac1. Furtherexperiments demonstrated that knockdown of TIAM2 could up-regulate the expression of E-cadherin, and downregulatethe expression of MMP-3, Twist and Snail. Conclusions: Our data suggest that TIAM2 can promoteinvasion and motility of NSCLC cells. Activation of Rac1 and regulation of some EMT/invasion-related genesmay be involved in the underlying processes.