To further investigate the potential roles of RBP2 in tumor angiogenesis, we provide evidence showing that high RBP2 expression in NSCLC cell lines significantly promotes tumor angiogenesis and elucidate the mechanism involved in the activation of Akt signaling, induction of HIF-1α protein accumulation and VEGF expression under normoxia. The gene discussed is RBP2; the disease is neoplasm.