A novel polydimethylsiloxane/liquid crystal cross-linked membrane (PDMS/LC) was prepared by using PDMS containing vinyl groups and LCs containing unsaturated linkages as matrix materials. Mechanical properties, liquid crystalline performance and blood compatibility of the PDMS/LC cross-linked membrane containing different LC contents and LC groups were investigated, respectively. The results showed that mechanical properties of the membrane increased more significantly than those of pure PDMS membranes. The PDMS/LC cross-linked membrane also possessed better membrane-forming ability, lower hemolysis rate, less platelets adhesion and more favorable anti-coagulant properties. Additionally, mechanical properties and blood compatibility of the membrane can be enhanced simultaneously and obviously due to the introduction of the cholesteric liquid crystals and the application of the preferred cross-linked reaction without byproducts.