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An excellent moisturizer, hyaluronic acid (HA(, provides biocompatibility and viscoelastic properties that is extensively utilized in cosmetics. High molecular weight HA (HMW-HA, 1.2 MDa( is a typical used form, however its benefits is limited due to its large molecule. In our previous study, the association with quaternized cyclodextrin grafted chitosan (QCD-g-CS( can improve skin penetration and provide positive charge promoting skin adhesion. Thus, the purpose of this study was to produce and characterize HMW-HA associated QCD-g-CS nanoparticles for cosmetic utilization. The HMW-HA nanoparticles (0.01 HA per 1 QCD-g-CS mole ratio( was the best formula with low particles size (348.20 ± 8.67 nm(, narrow polydispersity index (0.083 ± 0.02(and positive zeta potential (16.00 ± 0.36 mV(. The association efficiency and loading efficiency were analyzed by UPLC and shown to be 82.64 ± 0.39% and 20.09 ± 0.57%, respectively. The conjugation between carboxylic moieties of HMW-HA and amide of QCD-g-CS was confirmed by FTIR. The TEM imaging showed the spherical morphology of these nanoparticles. According to cytotoxicity test, these nanoparticles (0.01 to 0.10 mg/ml( were safe in human skin fibroblasts.