OBJECTIVE: To establish a method for the content determination of main ingredient in naproxen solid lipid nanoparticles. METHODS: Microemulsion method was used to prepare naproxen solid lipid nanoparticles, and HPLC was used for the content determination. The column was Elite C18 with mobile phase A of methanol and B of 0.01mol/L KH2PO4 buffer solution (adjust pH to 3.0 by phosphoric acid)(gradient elution) at a flow rate of 1.0 ml/min, detection wavelength was 240 nm, column temperature was 25 ℃,and injection volume was 20 μl. RESULTS:The linear range of naproxen was 0.2-180.0 μg/ml(r=0.999 7); RSDs of precision, stability and reproducibility were lower than 1.00%; recovery was 99.73%-100.29%(RSD=0.20%,n=9). CONCLUSIONS: The method is simple, accurate, and can exclude the accessories’ interference in naproxen solid lipid nanoparticles, which is suitable for the content determination of main ingredient.