Background:Polymethyl Methacrylate (PMMA) denture-base resins have poor surface properties that facilitates microbial adhesion causing denture stomatitis. This systematic review aims to evaluate the effect of different sizes and percentages of titanium dioxide nanoparticles (TiO2NP) on the antimicrobial property, surface roughness and surface hardness of PMMA denture base resin.Methods:A systematic search of English peer-reviewed articles, clinical trial registries, grey literature databases and other online sources was performed using the PRISMA-S Guidelines forIn-VivoandIn-Vitrostudies. Qualitative data synthesis was performed to analyse sample dimensions, acrylic used, treatments of nanoparticles, methods used for testing and effect of size and percentage of nanoparticle. Risk of bias assessment was done using modified Cochrane risk of bias tool.Results:Out of 1376 articles, 15 were included. TiO2NP of size less than 30 nm was most frequently used. Both antimicrobial property and surface hardness improved irrespective of the size of the added TiO2NP. Three studies reported increase in the surface roughness with less than 50 nm TiO2NP.  3% TiO2NP was most frequently used. On increasing the percentage, three studies reported an increase in antimicrobial property, while two studies found no change. With TiO2NP greater than or equal to 3%, six studies reported an increase in surface hardness, while two reported increase in surface roughness. Large methodological variations were observed across studies. All studies except one were of moderate quality.Conclusions:On addition of TiO2NP to heat polymerized PMMA, the antimicrobial property and surface hardness improved irrespective of the size of the TiO2NP, however, addition of nanoparticles less than 50 nm increased the surface roughness. Increasing the percentage of TiO2NP increased the surface hardness but did not always increase the antimicrobial property. Addition of 3% TiO2NP provided optimum results with regards to antimicrobial effect and surface hardness, but increase in the surface roughness.