In order to improve the bioavailability and stability of fat soluble lycopene, lycopene nanostructured lipid carriers were prepared by melting high-speed shear method. Taking the entrapment efficiency and average particle size as the main evaluation indexes, the single factor test was carried out, and the preparation process was optimized by genetic algorithm combined with Box-Behnken response surface method. The theoretical entrapment efficiencies optimized by genetic algorithm and Box-Behnken response surface method are 86.208 2% and 86.169 5%. By validation test, the actual entrapment efficiency and average particle size were (86.267±0.44)% and (121.8±5.20)nm. The results show that the optimization of lycopene nanostructured lipid carrier model by genetic algorithm combined with Box-Behnken response surface method is reliable.