Abstract The bone formation is considered to be accompanied by the piezoelectric effects in bone. Therefore, the piezoelectric effect under ultrasound irradiation should be elucidated to realize the effective healing. Then, the piezoelectric properties in cancellous bone have been attempted to clarify by complementing experiments and simulations with each other. In this paper, the piezoelectric signals generated in water-saturated cancellous bone by ultrasound irradiation were experimentally and numerically observed, and the effect of the trabecular orientation was investigated. The experimental observation was performed by the piezoelectric cell (PE-cell), which corresponds to an ultrasound receiver using the cancellous bone specimen as a piezoelectric element. The numerical observation was performed by the piezoelectric finite-difference time-domain (PE-FDTD) method, which is an elastic FDTD method with piezoelectric constitutive equations. In both the experimental and simulated results, the piezoelectric signal amplitude increased with the mean intercept lengths (MILs) of the trabecular elements and the pore spaces or the strength of the trabecular orientation. From the fact that the ultrasound propagation in water-saturated cancellous bone can depend on the trabecular orientation, it was considered that the ultrasound properties could be largely associated with the piezoelectric properties.