The sensing efficiency or factor of noble metal nanoparticles is defined as the wavelength shift of the surface plasmon resonance extinction peak position per unit change in the refractive index of the surrounding medium. The sensitivity of different shapes and sizes of gold nanoparticles has been studied by many investigators and found to depend on the plasmon field strength. As a result, the sensitivity factors were found to be larger for hollow nanoparticles than for solid ones of comparable dimensions. This is due to the strong plasmonic fields resulting from the coupling between the external and internal surface plasmon fields in the hollow nanoparticles. In the present paper, the sensitivity factors of a large number of gold nanoframes of different size and wall thickness have been determined by experimental and theoretical computation (using the discrete dipole approximation method). The dependence of the sensitivity factors and the plasmon field strength on the wall thickness and the size of the nanoframes has been determined and is discussed. The sensitivity factors are found to increase linearly with the aspect ratio (wall length/wall thickness) of the nanoframes and are especially sensitive to a decrease in the wall thickness. In comparison with other plasmonic nanoparticles, it is found that nanoframes have sensitivity factors that are 12, 7, and 3 times higher than those of gold nanospheres, gold nanocubes, and gold nanorods, respectively, as well as more than several hundred units higher than those of comparable-size gold nanocages.