The current study tested expression and potential function of circular RNA ecto-5’-nucleotidase (circNT5E) in human non-small cell lung cancer (NSCLC). We show that circNT5E levels are significantly elevated in human NSCLC tissues and cells, correlating with downregulation of its potential targets, miR-134, miR-422a and miR-338. In A549 and primary NSCLC cells, circNT5E shRNA inhibited cancer cell growth, proliferation and migration, whiling inducing apoptosis activation. Conversely, ectopic circNT5E overexpression promoted A549 cell progression in vitro. miR-134 is the primary target of circNT5E in lung cancer cells. RNA-Pull down assay in A549 cells confirmed the direct association between biotinylated-miR-134 and circNT6E. miR-134 levels were significantly increased in circNT5E-silenced A549 cells, but reduced with circNT5E overexpression. Forced overexpression of miR-134 mimicked circNT5E shRNA-induced actions, inhibiting NSCLC cell growth and proliferation. In contrast, miR-134 inhibition largely attenuated circNT5E shRNA-induced anti-NSCLC cell activity. Importantly, circNT5E shRNA was ineffective in miR-134-overexpressed A549 cells. Collectively, circNT5E promotes human NSCLC cell progression possibly by sponging miR-134.