Considering mass transfer and energy transfer between liquid phase and vapor phase, a mixture model for boiling heat transfer of nanofluid is established. In addition, an experimental installation of boiling heat transfer is built. The boiling heat transfer of TiO2–water nanofluid is investigated by numerical and experimental methods, respectively. Thermal conductivity, viscosity, and boiling bubble size of TiO2–water nanofluid are experimentally investigated, and the effects of different nanoparticle mass fractions, bubble sizes and superheat on boiling heat transfer are also discussed. It is found that the boiling bubble size in TiO2–water nanofluid is only one-third of that in de-ionized water. It is also found that there is a critical nanoparticle mass fraction (wt.% = 2%) between enhancement and degradation for TiO2–water nanofluid. Compared with water, nanofluid enhances the boiling heat transfer coefficient by 77.7% when the nanoparticle mass fraction is lower than 2%, while it reduces the boiling heat transfer by 30.3% when the nanoparticle mass fraction is higher than 2%. The boiling heat transfer coefficients increase with the superheat for water and nanofluid. A mathematic correlation between heat flux and superheat is obtained in this paper.