Abstract: With the increase of the concentration of dodecyl trimethyl ammonium bromide (DTAB), hyaluronic acid (CA-HA) hydrophobically modified with cinnamic acid forms four kinds of CA-HA/DTAB complexes (I、II、III、IV) through electrostatic and hydrophobic interactions. The formation and transformation mechanisms of CA-HA/DTAB complexes with different structures have been studied by means of transmission electron microscopy, dynamic light scattering, Zeta potential measurement and UV absorption spectroscopy. CA-HA/DTAB (I) is formed by the electrostatic attraction between the positively charged headgroup of DTAB and the negatively charged carboxyl groups in CA-HA. The hydrophobic aggregation of the DTAB alkyl chain causes the molecular chain of CA-HA to cross-link, leading to the transformation of CA-HA/DTAB (I) into CA-HA/DTAB (II). In CA-HA/DTAB (III), DTAB forms micelles on the molecular chain of CA-HA. The electrostatic repulsion between DTAB micelles disintegrates CA-HA molecular chains to form CA-HA/DTAB (IV). Through a permeation experiment on the surface of phospholipid membrane, it is found that the permeation rate and equilibrium cumulative permeation amount of CA-HA in CA-HA/DTAB (I) were 2 times and 1.5 times those of pure CA-HA, respectively, and CA-HA in CA-HA/DTAB (II), CA-HA/DTAB (III), and CA-HA/DTAB (IV) have almost no permeation ability. The different permeability of CA-HA/DTAB (I), CA-HA/DTAB (II), CA-HA/DTAB (III), and CA-HA/DTAB (IV) is rationalized. Because of a small particle size and high flexibility, CA-HA/DTAB (I) renders CA-HA more permeable, and its equilibrium cumulative permeation amount on the phospholipid membrane surface is higher than that of pure CA-HA. Due to the large aggregation structures of CA-HA/DTAB (II) and CA-HA/DTAB (III), CA-HA is not able to penetrate the phospholipid membrane. CA-HA/DTAB (IV) can clog the phospholipid membrane pore by forming a film on the membrane surface, which can thoroughly inhibit the permeation of CA-HA through the phospholipid membrane surface.