We successfully developed a novel method for immobilizing poly(2-methacryloyloxyethyl phosphorylcholine) [Poly(MPC)] polymer onto collagen using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) as cross-linkers. In order to obtain the highest possible molar ratio of immobilized MPC moieties on the collagen gel, a collagen-phospholipid polymer hybrid gel was prepared by repeating the cross-linking process up to three times to create a dense network of collagen and PMA. Network formation by repeating the immobilization process was successful, resulting in decreased free amine group content and a low swelling ratio. The hybrid gel displayed very high stability against degradation by collagenase and possessed high hydrophilicity. Fibrinogen adsorption and cell adhesion were reduced and demonstrated less cell proliferation as compared to that by uncross-linked collagen gel. The collagen-phospholipid polymer hybrid gel did not exhibit toxicity, and the cell morphology remained intact (round); this implies that the interaction between the cell and the collagen-phospholipid polymer hybrid gel is safe and mild.