Objective To optimize the formulation of curcumin loaded nanostructured lipid carriers by Box-Behnken design and investigate its physic-chemical properties.Methods Curcumin loaded nanostructured lipid carriers were prepared by film-dispersion and ultrasonication method.A three factor,three-level Box-Behnken design was employed,with the amount of the drug concentration(X1),mixed lipid(X2) and emulsifier mixture concentration(X3) as the investigation object.The evaluation indexes were the entrapment efficiency particle size(Y1) and particle size(Y2).Transmission electron microscopy(TEM) was employed to study the shape.Dynamic light scattering was used to study the particle size and electric potential.The entrapment efficiency was determined by mini-column centrifugation.Results In the optimized formulation,the shape of NLC was round or ellipsoidal with the particle size of(58.37 ± 2.60)nm,the many dispersion index(P.I.) was 0.207,entrapment efficiency was(93.48 ± 0.86)% and Zeta potential was-(22.6 ± 0.88)mV.DSC showed that the drug was dispersed in the nanoparticles of non-crystalline.Conclusions The Box-Behnken design is effective and suitable for optimizing the formulation of curcumin loaded nanostructured lipid carriers.