Docetaxel (DTX) proved one of the most effective active pharmaceutical ingredients (APIs) for the treatment of cancers. However, in respect of its low solubility and high lipophilic property, nicotinamide (NCT) was chosen as the co-former to form the docetaxel-nicotinamide complex to handle the drawbacks. As was analyzed by Fourier Transform Infrared spectrometer, thermal analysis and saturated solubility, the complex proved stable. Then, docetaxel-nicotinamide complex nanostructured lipid carriers (DN-NLCs) were prepared by emulsion-evaporation at low temperature method. The average drug entrapment efficiency, particle size and drug loading of docetaxel-NLCs (D-NLCs) and DN-NLCs were 81.41-79.48%, 61.45-59.48nm and 1.60-1.63%, respectively. The physicochemical characteristics of nanoparticles were valued by transmission electron microscope and Powder X Ray Diffraction. The in vitro drug-release profile of nanoparticle formulations fitted the Weibull dynamic equation. The skin permeability test was performed by Vertical Franz-type diffusion cells. It demonstrated that DN-NLCs transported drugs more easily than D-NLCs. Confocal Laser Scanning Microscopy observation showed DN-NLCs permeated more effectively than D-NLCs. In vivo study demonstrated that DN-NLCs maintained most in the skin. These results suggest that the DN-NLCs can be a useful method to increase skin permeation of docetaxel.