objectives: To investigate the effects of ZrO2 volume fraction on the mechanical properties of novel dental PMMA- ZrO2 biomimetic nanocomposites. Methods: Partially sintered Zirconia ceramics (PSZCs) with different density were prepared via isostatic pressing and partially sintering at different temperature, with Zirconia nanopowder as raw materials. Then PMMA-Zirconia composites (PZCs) with different ZrO2 volume fraction were prepared by vacuum infiltrating the prepolymerized MMA into these PSZCs, followed by in-situ polymerization. The PZCs which ZrO2 volume fraction were 65%, 70%, 75%, 80%, named PZC-65%, PZC-70%, PZC-75%, PZC-80%.Then bending strength, fracture toughness and Vickers' hardness of these PZCs samples were measured. PZC blocks with size 10mm*12mm*15mm were machined on dental CAD/CAM(computer aided design/computer aided manufacture) system to manufacture a premolar crown, and the machining time were recorded. Results: The bending strength of PZC-65%, PZC-70%, PZC-75%, PZC-80% were 161.28MPa, 202.18MPa, 258.23MPa, 287.21MPa, respectively; the fracture toughness were 3.72MPa.m1/2, 4.30MPa.m1/2, 4.64MPa.m1/2, 4.75MPa.m1/2, respectively; Vickers' hardness were 1.95GPa, 3.60GPa, 4.40GPa, 5.12GPa, respectively; The machining time were 13.10min, 16.21min, 19.35min, respectively. PZC-80% couldn't be machined on dental CAD/CAM. Conclusions: The mechanical properties of PZCs were obviously influenced by ZrO2 volume fraction. The results indicated that the machinability of PZC-65%, PZC-70% and PZC-75% were good, the hardness of PZC-70% similar to tooth enamel. Fracture toughness and bending strength of PZCs were higher than those of traditional machinable dental porcelain. Maybe PZCs can be used as novel machinable materials for dental CAD/CAM.