OBJECTIVE: To prepare Salinomycin nanostructured lipid carriers (Sal-NLCs) and optimize its formulation. METHODS: Sal-NLCs was prepared by emulsion evaporation-low temperature solidification method. Using particle size, Zeta potential, encapsulation efficiency and drug loading as evaluation indexes, central composite design-response surface methodology was used to optimize the amount of Sal, the ratio of solid lipid glyceryl bisstearate to liquid lipid glyceryl octanoate in oil phase, ratio of surface active agent polyoxyethylene 35 castor oil (EL) to polyethylene glycol-15-hydroxy stearate (HS 15), the amount of polyoxyethylene (40) stearate (P40). The morphology, particle size, polydispersity index (PDI), Zeta potential, encapsulation efficiency, drug loading and in vitro release mechanism of Sal-NLCs were investigated. RESULTS: The optimal prescription was as follows as Sal 0. 86 mg, glyceryl bisstearate 40.70 mg, glyceryl octanoate 11.30 mg, EL 44.05 mg, HS15 7.95 mg, P40 3.8 mg. Prepared Sal-NLCs was round-like and dispersed evenly. The particle size, PDI, Zeta potential, encapsulation efficiency and drug loading of prepared Sal-NLCs were(81.81 ± 2.60) nm, 0.183 ± 0.042, (-24.9 ± 3.4) mV,(94.35 ± 1.50)％ and (1.47 ±0.04)％ (n=5), respectively.24 h accumulative release rate was (99.81 ± 3.90)％ (n=3).Drug release behavior was in line with Higuchi model, and relative error of particle size, Zeta-potential, encapsulation efficiency and drug loading to predicted value of model were all lower than 4％. CONCLUSIONS: Sal-NLCs with sustained-release effect is prepared successfully according to optimized formulation, and its quality meets the expected standard.