Aiming at the optimization of sensors’ number and locations in active control of structural response, an existing optimization selection method was improved. The method can effectively reduce the number of sensors and find their relevant optimization locations, at the same time the effect of vibration reduction maintains almost the same as before, and the control scale of hardware can be reduced distinctly. The optimization procedure was resolved with the genetic algorithm. In order to eliminate the coupling between multi-channel in active control, FxLMS algorithm was used. Four hydraulic actuators were placed between the floating raft and the hull structure, and the error signals were used as feedback signals for each actuator simultaneously, while using the improved integer coding genetic algorithm, the experimental research of active vibration isolation of multiple excitation frequencies was studied. Experimental results show that the effect of vibration reduction of 4 error signals maintains almost the same as that of 22 error signals, sound pressure of the 10 monitoring microphones were effectively suppressed.