Materials used for biomedical applications are required to have suitable surface properties since they depend more on the surface properties than on the bulk properties. Surface properties greatly influence the cell adhesion and its behavior either directly by guiding cell spreading or indirectly by controlling proteins adsorption and their structural rearrangement on the material. Modulation of physical and chemical properties of polymers by various treatments can render the substrates adhesive for cells in a culture. In the present study, polypropylene surface was modified using helium plasma to enhance cell adhesion to its surface. The experiments were run according to the central composite design of response surface methodology to optimize the process conditions. The effects of the process variables, namely, RF power, pressure, flowrate and treatment time on surface energy and percentage weight loss were studied through central composite design (CCD). A statistical model relating the process variables and the responses was developed. The improved hydrophilicity of polypropylene through helium plasma treatment was observed from its surface energy data. Changes in surface chemistry and surface morphology were studied by Fourier transform infrared spectroscopy and scanning electron microscopy, respectively. Enhanced cell adhesion to polypropylene treated with helium plasma at the optimum conditions, obtained from the statistical design, was observed from cell adhesion test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay with L929 mouse fibroblast cells. © 2009 Koninklijke Brill NV, Leiden.