Accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression and are involved in various pathological processes. In our present study, we firstly evaluated lncRNA LINC00152 and EGFR expressions by ISH or IHC methods, and analyzed the correlation between LINC00152 and EGFR with RT-PCR. lncRNA LINC00152 of NSCLC tissues were significantly up-regulation compared with adjacent normal tissues and positively correlated with EGPR. The further cell experiments demonstrated that Linc00152 knockdown had effects of suppression cell proliferation, invasion and migration abilities and improving cell apoptosis and G1 phase rates in both A549 and H1299 cell lines. In the mechanism study, the results were shown that EGFR, PI3K, AKT, Fibronectin and Vimentin proteins expressions were significantly reduced and P21 protein expression was significantly increased in Linc00152 knockdown groups. Our results suggested lncRNA LINC00152 knock-down had anti-tumor effects via EGFR/PI3K/AKT pathway.