The aim of this study was an synthesis of hydroxyapatite (HA) on cellulose fibers to be used as a new reinforcing agent for dental restorations. The microwave irradiation method was used for synthesis and the materials were characterized with analytical techniques. The prepared dental resin composites were mechanically tested by a universal testing machine and electrodynamic fatigue testing system. FTIR, XRD, SEM/EDS analysis confirmed the successful synthesis of HA on cellulose fibers. The Alamar blue biocompatibility assay showed more than 90% cell viability for the prepared cellulose/HA. The mechanical properties of resin composites improved with cellulose content from 30 wt.% to 50 wt.% in the polymer matrix. Substantially, increasing the cellulose/HA content from 40% to 50% improved the mechanical properties. The results suggested that HA could be successfully synthesized on cellulose fibers using microwave irradiation and contributed to improving the mechanical properties of dental resin composites.