Nanostructure-based surface plasmon resonance (SPR) sensors are capable of sensitive, real-time, label-free, and multiplexed detection for chemical and biomedical applications. Recently, the studies of nanostructure-based aluminum sensors have attracted a large attention. However, the intrinsic properties of aluminum metal, having a large imaginary part of the dielectric function and a longer electromagnetic field decay length, limit nanostructure’s surface sensing capability. To improve the surface sensitivity, a nearly guided wave SPR sensor has been proposed, which enables the surface plasmons to spread along the dielectric layer and increases the interaction volume. Here we proposed the combination between Fano resonances in capped nanoslits and a thin nanodielectric top layer to develop highly sensitive nanostructure-based aluminum sensors. We studied the effects of an Al2O3 protection layer on the optical properties, bulk and surface (wavelength and intensity) sensitivities of capped aluminum nanoslits. We found the top layer can enhance the sensitivities of the Wood’s anomaly-dominant resonance or asymmetric Fano resonance in capped aluminum nanoslits. The maximum improvement can be reached by a factor of 16. The maximum wavelength and intensity sensitivities are 6.8 nm/nm and 150 %/nm, respectively. With 1.71 % intensity change (3 times of noise level), the limit of detection of Al2O3 film thickness was 0.018 nm. We attributed the enhanced surface sensitivity for capped aluminum nanoslits to a reduced evanescent length and sharp slope of the asymmetric profile caused by the capped oxide layer and Fano coupling. The protein-protein interaction experiments verified the high sensitivity of the Al2O3-aliminum capped nanoslits.