In this study, we demonstrated a new molecular mechanism by which Nm23-H1 can affect lung cancer progression, wherein Nm23-H1 increases Sp1 expression during lung cancer progression by affecting the IRES-mediated translational activity through stabilizing the protein stability of hnRNPA2/B1; these functions imply that Nm23-H1 upregulation in the early stages of lung cancer and downregulation in the late stages of lung cancer might contribute to the Sp1 level during lung cancer progression. Here, SP1 is linked to lung cancer.