Highly open, porous polymer or poly(high internal phase emulsion) (polyHIPE) obtained from polymerized high internal phase emulsions (HIPE) have recently attracted much attention and increasing interest in tissue engineering applications because of their excellent properties. This research is aimed at preparing and developing a process for producing polyHIPE for use as a scaffold in tissue engineering applications. Poly(styrene/ethylene glycol dimethacrylate) (poly(S/EGDMA)) loaded with hydroxyapatite was used to prepare the polyHIPE. Further improvement on hydrophilicity and biological response to tissue fluids of the polyHIPE porous polymer was carried out using a nanolayer coating via the layer-by-layer polyelectrolyte multilayer (PEM) technique. Three types of chemicals were used for coating on the surface of the polyHIPE porous polymer such as poly(sodium 4-styrene sulfonate) (PSS), gelatin (GEL), and alginic acid (ALG). The change in surface properties of the modified poly(S/EGDMA)HIPE was characterized by UV-visible spectroscopy and contact angle measurement. Further assessments consisted of cytotoxicity testing, cell attachment, and proliferation of L929, fibroblast-like cells that were seeded on the surface of the polyHIPE porous polymer. A three-dimensional structure poly(S/EGDMA)HIPE porous polymer with high porosity was successfully prepared. Moreover, it was found that surface modification encouraged poly(S/EGDMA)HIPE with a hydrophilic nanolayer, as observed by the decrease in contact angle degree and cell adhesion of L929 fibroblast-like cells, indicating that the poly(S/EGDMA)HIPE porous polymer was effectively improved by using the layer-by-layer technique. It was revealed by MTT assay that the poly(S/EGDMA)HIPE porous polymer coated with a nanolayer of a polyelectrolyte multilayer led to an enhancement in the amount of cell adhesion and proliferation on the modified poly(S/EGDMA)HIPE porous polymer. Additionally, the most effective polyelectrolyte solution for improving cell adhesion of the poly(S/EGDMA)HIPE was PSS.