Mixed micelles made of polyvinylpyrrolidone (PVP), sodium cholate, and phospholipids were prepared to improve the solubility of poorly water-soluble drugs. Sylibin, a drug used in treating liver diseases, was incorporated into the mixed micelles. The formulation of sylibin containing PVP-sodium cholate-phospholipid mixed micelles with an optimized composition (PVP/sodium cholate/phospholipid/silybin = 3:3:4:1~2 by weight) was obtained based on the study of pseudoternary phase diagrams. The critical micelle concentration was used to evaluate the micellar stability towards dilution. The results showed that addition of PVP to sodium-cholate-phospholipid mixed micelles increased stability. The solubility of sylibin in PVP-sodium cholate-phospholipid mixed micelles was higher than that in pure water or in sodium cholate-phospholipid mixed micelles. In a stability study, we found that PVP-sodium cholate-phospholipid mixed micelles showed good stability. After 3 months storage at 40oC, just 2.6% sylibin was lost with only minor changes of the particle size when compared to a reference formulation containing sodium cholate and phospholipid mixed micelles. In addition, the developed formulation significantly improved in vitro drug release. The time required to release 50% sylibin (t50%) from sodium cholate and phospholipid mixed micelles was 326 h, while the t50% from PVP-sodium cholate-phospholipid mixed micelles was only 51.1 h. Our results suggest that these mixed micelles might have significant potential application to the biomedical field.