Abstract: Recently, there is a great interest in the replacement of commercial bis-GMA resin matrix system for dentistry. Bis-GMA is considered to be relatively cytotoxic and allergenic to human. A novel resin matrix system based on HDDMA is under investigation. This study aimed to determine the biological property especially the cytotoxicity property of proposed HDDMA-based resin matrix systems of FRCs material toward fibroblast cells. Fifteen FRCs specimens were prepared and divided into 3 groups. Two groups were based on HDDMA matrix systems and one group was bis-GMA-based. The cytotoxicity property was determined by MTT method. The result revealed significant differences in cells viability between HDDMA-based matrices and bis-GMA-based, whilst no significant difference between the two proposed HDDMA-based matrices. In conclusion, proposed resin matrix systems based on HDDMA exhibited a less cytotoxic material than bis-GMAbased.