INTRODUCTION: The purpose of this study was to develop a novel dental resin composite by integrating polyhedral oligomeric silsesquioxane (POSS) with zirconia modified by 10-methacryloxydecyl dihydrogen phosphate (10-MDP). METHODS: The resin matrix was synthesized in dark conditions. The experimental groups were designated based on the content of POSS incorporated into the resin matrix, with a concentration range of 2 wt% to 8 wt%. After thoroughly mixing the resin matrix, 5 wt% zirconia treated with 10-MDP was added. RESULT: The FTIR spectra showed the appearance of new absorption bands, and the XPS(X-ray Photoelectron Spectroscopy) study confirmed the effectiveness of the surface treatment of zirconia. The resin composite exhibited optimal properties at a POSS concentration of 4 wt%, with significant improvements in flexural strength, compressive strength, and Vickers hardness compared to the control group. However, these properties decreased when the concentration exceeded that of the 4 wt % group. The incorporation of POSS significantly reduced the polymerization shrinkage of the resin composite. Moreover, none of the experimental resin composites exhibited cytotoxicity, indicating excellent biocompatibility. CONCLUSION: We have succeeded in developing a new resin composite that significantly improves its performance when POSS is added at a concentration of <
4wt%, and reaches its optimum level at a concentration of 4wt%. CLINICAL SIGNIFICANCE: The development of this novel resin composite provides a new material option for clinical applications. The improved properties from this work show potential for developing an alternative material for clinical application.