Aim: The purpose of this study was to evaluate the effect of Zirconium oxide (ZrO2) nanofillers powder with different concentration (1.5%, 3%, 5% and 7%) on the transverse strength and impact strength of heat-polymerized acrylic resin. Materials and Methods: Zirconium oxide powders with different concentrations (1.5%, 3%, 5% and 7%) were incorporated into heat-cure acrylic resin (PMMA) and processed with optimal condition (2.5:1 Powder/monomer ratio, conventional packing method and water bath curing for 2 hours at 95˚C) to fabricate test specimens of PMMA of dimensions (65 x 10 x 2.5mm) for the transverse strength and (60 x 7 x 4mm) for impact strength. PMMA without additives was prepared as a test control. Two types of mechanical tests; transverse strength and impact strength were carried out on the samples. The recorded values transverse strength in (MPa) and impact strength in (J) were collected, tabulated and statistically analyzed. One way analysis of variance (ANOVA) and Tukey's tests were used for testing the significance between the means of tested groups which are statistically significant when the P value ≤ 0.05. Results: Addition of Zirconium oxide nanofillers to PMMA significantly increased the transverse strength and impact strength Conclusion: Zirconium oxide nanofillers added to PMMA has a potential as a reliable denture base material with increased transverse strength and impact strength. According to the results of the present study, the best mechanical properties were achieved by adding 7%wt ZrO2 concentration.