Objective To investigate the pharmacokinetic characteristics of asparaginase-loaded sulfobutyl ether-β-cyclodextrin supramolecule lipidic nanoparticles (ASLN) in rats and its inhibitory effect on the proliferation of small cell lung cancer cells. Methods ASLN were prepared by a reverse phase evaporation method, and their physicochemical properties, including morphology, particle size, zeta potential, and drug entrapment efficiency, were characterized. Twelve male Sprague-Dawley rats were randomly divided into 2 groups, with 6 rats in each group. After intravenous injection of ASLN and free asparaginase (Aase) 2 kU/kg, the activity of Aase in plasma samples was measured at different time points in 48 h, and the activity-time curve was drawn. The pharmacokinetic parameters were calculated by software DAS 2.1.1. The cytotoxicity of ASLN on H446 cells was explored by the MTT method. Results ASLN showed a spherical shape with a mean particle size of (321.27±1.42) nm, zeta potential of (－9.31±0.42) mV, and entrapment efficiency of (66.46±1.57) %. Pharmacokinetic parameters of ASLN and Aase were as follows: the area under curve (AUC_{(0-48 h)}) (199.48±2.18) U·mL^－1·h, (57.63±3.89) U·mL^－1·h; the mean residence time (MRT_{(0-48 h)}) (4.40±0.05) h, (2.09±0.07) h; and the peak concentration (C_max) (35.49±1.11) U/mL, (27.58±1.28) U/mL. The relative bioavailability of ASLN to Aase was 325.96%. The cytotoxicity results indicated that ASLN had a proliferation inhibitory effect on H446 cells, and there was a positive correlation between the inhibition rate and the dose. Conclusion ASLN can improve the pharmacokinetics of Aase, enhance the bioavailability of Aase, and inhibit the proliferation of small cell lung cancer cells.