Based on the Khokhlov-Zabolotkaya-Kuznetsov (KZK) equation in frequency-domain, a theoretical model of focused ultrasonic waves in the layered biological medium with consideration of the sound absorption, nonlinearity, boundary of the media and the diffraction of the source is presented. The propagation of focused ultrasonic waves for fundamental and second harmonic in the multi-layered biological media are numerically studied and compared with the experimental results. Good agreement of the theory with the measurement shows that this approach can effectively describe the second harmonic sound field in multi-layered biological media.