According to the ultrasonic propagation characteristics in the multi-medium, a control method of ultrasonic focus in the multi-medium is presented through introducing the phase compensation factors and using genetic algorithm. The patterns of multi-focus ultrasonic field generated by two-dimensional phased array consisting of 1616 elements are simulated in multi-biological tissue, and the ultrasonic fields are calculated under the various thicknesses and the various absorption coefficients of medium layer. The results show that this approach can optimize the patterns of multi-focus ultrasonic field and restrain side-lobe, which can improve the ultrasonic intensity gain and make the maximal ultrasonic intensity focus on the target area. When the thickness and the absorption coefficient of biological tissue are changed, the focus position remains unchanged, but the ultrasonic intensity of the focus area will change relatively.