The growth and aggregation of calcium oxalate monohydrate (COM) crystals beneath dipalmitoylphosphatidylcholine (DPPC) monolayers in the presence of chondroitin sulfate A (C 4 S) was systematically examined under different surface pressure. The results indicated that the addition of C 4 S can inhibit the crystal growth and prevent the aggregation of COM crystals. Under a DPPC monolayer, well-defined three-dimensional hexagonal prisms and three-dimensional rhombus prisms with sharply angled tips were obtained. The DPPC monolayer at a surface pressure of 10mN/m can match the Ca 2+ distance of the (1¯01) face of COM better than at 20mN/m. The addition of C 4 S could cooperatively modulate the interaction strength between the monolayer (or itself) with the specific morphology determining faces such as (1¯01) and (020), and thus results in remarkable stabilization of the (1¯01) faces. The dramatic changes in morphological details were due to the strong electrostatic interactions between the Ca 2+ -rich (1¯01) crystal faces of COM and the polyanionic polysaccharide C 4 S together with the negatively charged sites of the zwitterionic DPPC monolayers. The increase of the concentration of C 4 S can further enhance the stabilization of the (1¯01) face.