In conclusion, using phage display peptide libraries to screen for peptides that bind to NSCLC cells, we identified several novel peptides including SP5-2 that specifically bound to the cell surface of NSCLC cells both in vitro and in vivo. Linking SP5-2 to liposomes containing doxorubicin and vinorelbine increased the therapeutic efficacy and survival rates in mice with human NSCLC xenografts because of enhanced tumor apoptosis and decreased tumor angiogenesis. Quantitation and visualization of doxorubicin levels also showed increased drug concentration in tumor tissues in this formulation, highlighting the enhancement in both the delivery and penetration of doxorubicin into the tumor. Our results indicate that the SP5-2 tumor targeting peptide may be used as imaging probes of NSCLC and targeting ligands for liposomal delivery systems to increase the efficacy of chemotherapy for NSCLC.