Dental resin-based composites have been used for more than 50years. The size and the structure of inorganic filler have a great effect on the mechanical properties of the composite resin. In this study, novel micro-sized clusters of hydroxyapatite nanorods (MCHN) were designed and conveniently fabricated by spray drying combined with heat treatment. The effects of the aspect ratio of primary hydroxyapatite nanorods (HN), suspension concentration for spray drying and heat treatment temperature were explored. The results indicated that HN with a lower aspect ratio of 2 (HN-2) and a heat treatment temperature of 500 degrees C were beneficial to the construction of high-performance MCHN (MCHN-2). As compared to HN-2, MCHN-2 had a further increased filling amount by 10%. More importantly, the flexural strength, flexural modulus and compressive strength of the composite resin were greatly improved by 36.3%, 11.4% and 56.6%, respectively. Therefore, it could be envisioned that MCHN could have a great potential in dental restorative application.