In the present study, for the first time, we demonstrated that overexpression of STAT3 or HIF-1α decreased the expression of miR-199a-5p in NSCLC cells, which indicated that the hypoxic tumor microenvironment and activation of STAT3 signaling contributed to the dysregulation of miR-199a-5p in NSCLC cells. The gene discussed is STAT3; the disease is neoplasm.