We demonstrated via real-time polymerase chain reaction that NEAT1 was significantly increased in NSCLC tissues and cell lines, suggesting a potential role of NEAT1 in NSCLC. CCK-8 assay and colony-formation assays showed that silencing of NEAT1 by siRNA pool inhibited NSCLC cell proliferation. An increased population of apoptotic cells was detected upon NEAT1 depletion by acridine orange/ethidium bromide staining compared to control cells. A549 cells depleted of NEAT1 exhibited reduced invasion and migration, characterized by wound healing assay and Transwell assay. To uncover the molecular mechanism of NEAT1 in lung cancer, we identified that NEAT1 could be a competing endogenous RNA against let-7a, and insulin-like growth factor (IGF)-2 could be a direct target of let-7a. These were characterized by reciprocal expression between NEAT1/IGF-2 and let-7a. Luciferase reporter assay validated direct binding of NEAT1/let-7a and let-7a/IGF-2. Exogenous IGF-2 expression reversed NEAT1-knockdown-induced growth inhibition assessed by CCK-8 assay and colony-formation assay.