Objective: To optimize the formulation and preparation technology of hydroxy safflower yellow A solid lipid nanoparticles and evaluate its quality. Metheds: Hydroxy safflower yellow A solid lipid nanoparticles were prepared by the method of hot melt emulsification ultrasonic-low temperature using hydroxypropyl methylcellulose as a lipid material and glyceryl monostearate as an emulsifier. Using entrapment efficiency as indexes, the amount of hydroxypropyl methylcellulose, purified water, glyceryl monostearate, and Tween 80 aqueous solution (1%) as factors, orthogonal test was applied to optimize the formulation and preparation technology. Dialysis method was used to measure encapsulation efficiency. The morphology and uniformity of the nanoparticles were observed by transmission scanning electron microscopy. The particle size, polydispersion index and Zeta potential were determined by nano-particle size analyzer. And hydroxy safflower yellow A solid lipid nanoparticles sustained releasing characteristics was evaluated by the percentage of cumulative drug release. Results: The optimal process of prepared hydroxy safflower yellow A solid lipid nanoparticles was 5 mg of hydroxypropyl methylcellulose, 0.2 ml of purified water, 100 mg of glyceryl monostearate, and 1.8 ml of Tween 80 aqueous solution (1%). The size of the prepared nanoparticles was uniform and spherical. And the average particle size were (99.85 ± 3.04) nm, polydispersion index were (0.390 ± 0.021), Zeta potential were (-27.63 ± 2.12) mV, and the encapsulation efficiency of the hydroxy safflower yellow A solid lipid nanoparticles were (63.35 ± 2.65)%. The release rate of the nanoparticles was (44.35 ± 0.49)%. Conclusions The prepared hydroxy safflower yellow A solid lipid nanoparticles have good uniformity and good sustained release properties.