Most drugs do not have the pharmacokinetic features required for optimal pulmonary delivery. In this study, we developed PEGylated nanostructured lipid carriers (PEG-NLCs) to improve the delivery of anti-tumour agents to lung tumours. PEG-40 NLCs modified with PEG-40 stearate (molecular weight 2000 Da), PEG-100 NLCs modified with PEG-100 stearate (molecular weight 5000 Da) and NLCs without PEG modification were prepared by melt-emulsification and homogenization, and were loaded with 10-hydroxycamptothecin (HCPT). They were investigated in terms of physiological characteristics, biodistribution, cellular uptake, and anti-tumour effect in-vivo. PEG-NLCs exhibited regular morphology, with a spherical shape. The particle size (measured by laser diffraction) was approximately 100 nm. Encapsulation in PEG-NLCs protected the active lactone form of HCPT compared with HCPT solution after incubation with plasma. In biodistribution studies, PEG-NLCs, especially PEG-40 NLCs, had longer circulation time and decreased uptake by the reticuloendothelial system (RES) compared with unmodified NLCs. PEG-NLCs accumulated in the lungs after i.v. injection in mice. PEG-NLCs showed enhanced cellular uptake by human lung adenocarcinoma epithelial A549 cells. In-vivo experiments indicated that PEG-NLCs loaded with HCPT have superior efficacy against A549 lung cancer compared with HCPT solution and NLCs. These results suggest that PEG-NLCs is a promising delivery system for HCPT in the treatment of lung cancer.