AIM: To investigate the role of translationally controlled tumor protein (TCTP) in lung cancer development. MAIN METHODS: A549 and HCC827 cells were transfected with shRNA specifically targeting TCTP mRNA. Cell growth was assessed by colony formation assay and cell counting kit-8. Cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion was measured by scratch and transwell assays. In vivo tumorigenicity was evaluated by tumor xenografts in nude mice. KEY FINDINGS: TCTP-silenced cells displayed a reduced ability of colony formation and a lower rate of proliferation in vitro. Knockdown of TCTP arrested cell cycle at G1 phase and led to downregulated expression of cyclins B1, D1 and E. Moreover, silencing of TCTP induced apoptosis and altered the levels of apoptosis-regulatory proteins such as cleaved caspase-3, Bcl-2, Bax and p53. Silencing of TCTP also inhibited migration and invasion of lung cancer cells. In addition, TCTP-silenced A549 cells, when subcutaneously inoculated in nude mice, formed tumors at a significantly slower rate. SIGNIFICANCE: Our in vitro and in vivo data indicate that silencing of TCTP inhibits growth, migration and invasion of lung cancer cells. Thus, TCTP may be a potential target for lung cancer therapy.