We have investigated feasibility of waveguide-mode sensors, which is sensitized by a nanocolumnar SiO2 waveguide layer deposited by an oblique angle deposition technique. Because the effective refractive index of nanocolumns and fluid composites (n1) depends on that of fluid (n2), sensitivity of the waveguide-mode sensors is expected to be improved. In fact, the resonant angle of incidence of the waveguide-mode sensors, which have various combinations of layer thicknesses, changes significantly depending on the analytes of air (n2 = 1.00), H2O (n2 = 1.33) and C2H5OH (n2 = 1.36). The effective refractive indices of the waveguide layer immersed in these fluid are estimated at 1.28 for air, 1.41 for H2O and 1.42 for C2H5OH. The effective refractive index of the waveguide layer is understood by Bruggeman’s effective medium model. Therefore, the nanocolumnar waveguide layer is quite useful to improve sensitivity of the waveguide-mode sensors. In order to improve sensing sensitivity, more porous layer is desirable.