This study was conducted to investigate the effect of adding silica nanoparticles on the physicochemical properties, antimicrobial action, and the hardness of dental stone type 4. Dental stone type 4 powder was physically mixed with nanoparticle powder at weight percentages (0, 0.5, 1, and 2 percent). The required amount of powder was added to water according to the manufacturer's instructions. The prepared set materials were subjected to the physicochemical studies; Fourier transmission infrared spectroscopy (FTIR) was taken up to investigate the functional groups and X-ray diffraction (XRD) was used to evaluate the crystallinity. Also, scanning electron microscopy (SEM) was used to examine the morphology of the prepared samples. Agar diffusion test was carried out for the prepared samples against the Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) to test the average growth inhibition zones. Finally, the Vickers surface hardness test was performed for each group using a hardness tester. The adding silica nanoparticles to dental stone type 4 increased the diameter of inhibition zones for the groups in both bacteria significantly (
p
< 0.05). The results showed that adding silica nanoparticles to dental stone type 4 increased the diameter of inhibition zones for the groups in both bacteria significantly (
p
< 0.0001). There was a significant difference between all groups and the 0% group in both bacteria (
p
< 0.0001). Besides, the adding of silica nanoparticles to dental stone type 4 increased the surface hardness significantly (
p
= 0.0057) without any effect on physicochemical properties. The 0% and the 0.5% groups had significant differences with the 2% group (
p
= 0.0046 and
p
= 0.0205 respectively). Then, at least 2% silica nanoparticles are needed for a significant increase. Clinical trials are needed to enlarge for dental stone type 4 containing silica nanoparticles in the future.